cancer and ayurveda

54
AYURVEDA and CANCER AYURVEDA and CANCER Dr. Rajesh Kotecha ‘Vaidya’ Dr. Rajesh Kotecha ‘Vaidya’ M.D. (Ayurveda) Chakrapani Ayurveda, Jaipur [email protected] [email protected] http://LearnAyurveda.com http://LearnAyurveda.com

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Page 1: Cancer and Ayurveda

AYURVEDA and CANCERAYURVEDA and CANCER

Dr. Rajesh Kotecha ‘Vaidya’Dr. Rajesh Kotecha ‘Vaidya’ M.D. (Ayurveda)

Chakrapani Ayurveda, Jaipur

[email protected]@ayu.in

http://LearnAyurveda.comhttp://LearnAyurveda.com

Page 2: Cancer and Ayurveda

IntroductionIntroduction Cancer is one of the commonest cause of death not only in is one of the commonest cause of death not only in

our country rather throughout the world.our country rather throughout the world.

Scientists and clinicians are working in many countries to find Scientists and clinicians are working in many countries to find out its etiopathogenesis and management. out its etiopathogenesis and management.

Though the incidence of cancer is more in developed Though the incidence of cancer is more in developed countries but developing countries also do not lag behind.countries but developing countries also do not lag behind.

Most of the patients in developing countries attend the Most of the patients in developing countries attend the hospital at a later stage, when little help could be provided to hospital at a later stage, when little help could be provided to them.them.

The present protocol of treatment like Radiotherapy and The present protocol of treatment like Radiotherapy and Multi chemotherapy are not available to many of them, Multi chemotherapy are not available to many of them, because of costlier drugs.because of costlier drugs.

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Page 3: Cancer and Ayurveda

Main disadvantage of these drugs or treatment is their Main disadvantage of these drugs or treatment is their cytotoxicity which not only destroys the cancer cells but cytotoxicity which not only destroys the cancer cells but also all other normal cells of the body.also all other normal cells of the body.

Many a time, the mortality becomes more due to these Many a time, the mortality becomes more due to these chemotherapeutic agents than to the disease itself.chemotherapeutic agents than to the disease itself.

Aim of combination of therapies using surgery, Aim of combination of therapies using surgery, radiotherapy, chemotherapy, hormonal and radiotherapy, chemotherapy, hormonal and immunotherapy is - to provide best possible palliation, immunotherapy is - to provide best possible palliation, relieving symptoms, slowing progress of the disease relieving symptoms, slowing progress of the disease resulting into increase in survival period.resulting into increase in survival period.

But the treatment does not always cure or eradicate But the treatment does not always cure or eradicate the diseasethe disease..

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Page 4: Cancer and Ayurveda

Ayurveda covers all the aspects of Ayurveda covers all the aspects of treatment modalities that too by treatment modalities that too by

establishing an equilibrium within the body.establishing an equilibrium within the body.

From phytotherapy to Anti-oxidants,From phytotherapy to Anti-oxidants, Panchakarma therapies for purification of Panchakarma therapies for purification of

body,body, Considering treating mind also andConsidering treating mind also and From palliation to prevention of adverse From palliation to prevention of adverse

effects of chemotherapy and radiotherapy,effects of chemotherapy and radiotherapy,

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Page 5: Cancer and Ayurveda

WHO about cancerWHO about cancer

WHO targeting to ease the global burden of WHO targeting to ease the global burden of cancer. Preventing cancer and raising quality of cancer. Preventing cancer and raising quality of life for cancer patients are recurring themes . life for cancer patients are recurring themes . Theme of this year world cancer day is Theme of this year world cancer day is CANCER CAN BE PREVENTED TOO. It CANCER CAN BE PREVENTED TOO. It includes reducing exposure to four common risk includes reducing exposure to four common risk factors. These are tobacco use, unhealthy diet, factors. These are tobacco use, unhealthy diet, physical inactivity & harmful use of alcohol. physical inactivity & harmful use of alcohol. According to WHO achievements in prevention According to WHO achievements in prevention & control of cancer, this will have a major & control of cancer, this will have a major positive impact not only on international health positive impact not only on international health but also on global development.but also on global development.

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Page 6: Cancer and Ayurveda

FACTS ABOUT CANCERFACTS ABOUT CANCER

It is leading cause of death worldwide.It is leading cause of death worldwide. lung cancer, stomach, liver, colon & breast lung cancer, stomach, liver, colon & breast

cancer causes most cancer death each cancer causes most cancer death each year.year.

About 30% cancer death can be About 30% cancer death can be prevented.prevented.

Prevention offers the most cost effective Prevention offers the most cost effective long term strategy.long term strategy.

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Page 7: Cancer and Ayurveda

Ayurveda and CancerAyurveda and Cancer

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Page 8: Cancer and Ayurveda

Ayurvedic view of cancerAyurvedic view of cancer

What WHO says today is already said in Ayurveda What WHO says today is already said in Ayurveda many years ago. The main aim of Ayurveda is many years ago. The main aim of Ayurveda is prevention. Ayurvedic literature defines three body prevention. Ayurvedic literature defines three body control system, viz. Vata, Pitta and Kapha. which control system, viz. Vata, Pitta and Kapha. which mutually coordinates to perform the normal function of mutually coordinates to perform the normal function of body. we can correlate benign neoplasm with one or body. we can correlate benign neoplasm with one or two of the body systems out of control. and is not too two of the body systems out of control. and is not too harmful because body is still trying to coordinate these harmful because body is still trying to coordinate these system. system.

Malignant tumors are very harmful because all three Malignant tumors are very harmful because all three major system lose mutual coordination and cause major system lose mutual coordination and cause tissue damage. In Ayurveda cancer resemblance to tissue damage. In Ayurveda cancer resemblance to Raktavaha, Rasavaha, Mansavaha, and Medovaha Raktavaha, Rasavaha, Mansavaha, and Medovaha strotodushta vyadhis.strotodushta vyadhis.

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Page 9: Cancer and Ayurveda

Possible correlation with modern terminology.Possible correlation with modern terminology.

PadminikantakaPadminikantaka KeloidKeloid Pandu / shoshaPandu / shosha LeukemiaLeukemia Medoja galagandaMedoja galaganda Hodgkin lymphomaHodgkin lymphoma ApacheApache Hodgkin diseaseHodgkin disease Aagantuja stanarogaAagantuja stanaroga CA of breastCA of breast Rakta gulmaRakta gulma Tumors of uterusTumors of uterus KachhapaKachhapa CA of palateCA of palate MamsatanaMamsatana Tumor of pharynxTumor of pharynx

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Page 10: Cancer and Ayurveda

Role of Ayurveda in cancer preventionRole of Ayurveda in cancer prevention

Ayurveda can be helpful in management of Ayurveda can be helpful in management of cancer in many ways as preventive, palliative, cancer in many ways as preventive, palliative, prophylactic, curative and supportive prophylactic, curative and supportive treatment. cancer prevention is targeted treatment. cancer prevention is targeted towards creating balance and harmony towards creating balance and harmony through diet, lifestyle, herbs, meditation, through diet, lifestyle, herbs, meditation, pranayama, yoga and cleansing the body of its pranayama, yoga and cleansing the body of its toxic load through an Ayurvedic specific toxic load through an Ayurvedic specific procedures known as Panchakarma.procedures known as Panchakarma.

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Page 11: Cancer and Ayurveda

According to Ayurveda any disease will According to Ayurveda any disease will occurs due to-occurs due to-

Asatymeindriyarthra sanyog (no use, Asatymeindriyarthra sanyog (no use, exploitation or wrong directional use of all exploitation or wrong directional use of all sense organs)sense organs)

Praghyaparadha (wrong application of Praghyaparadha (wrong application of intelligentsia)intelligentsia)

Kala (age or time factor)Kala (age or time factor)

To maintain healthy state one has to avoid To maintain healthy state one has to avoid these factors.these factors.

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Page 12: Cancer and Ayurveda

Management according to AyurvedaManagement according to Ayurveda

The therapeutic approach of Ayurveda has been divided The therapeutic approach of Ayurveda has been divided into four categories-into four categories-

Prakritisthapan chikitsa – Preventive aspectsPrakritisthapan chikitsa – Preventive aspects Roganashani Chikitsa – Cure of diseaseRoganashani Chikitsa – Cure of disease Rasayana chikitsa- Restoration of normal functionRasayana chikitsa- Restoration of normal function Naishthiki chikitsa – spiritual approachNaishthiki chikitsa – spiritual approach

Ayurveda can be helpful in the management of cancer in Ayurveda can be helpful in the management of cancer in many ways as prophylactic, palliative, curative and many ways as prophylactic, palliative, curative and

supportive and no doubt it helps to improve quality of life.supportive and no doubt it helps to improve quality of life. http://LearnAyurveda.comhttp://LearnAyurveda.com

Page 13: Cancer and Ayurveda

Ayurveda gives daily schedule (Dinacharya) Ayurveda gives daily schedule (Dinacharya) which is helpful to become healthy.which is helpful to become healthy.

Aachyara Vagbhata says,Aachyara Vagbhata says,

Ash.Ha.4/36Ash.Ha.4/36

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Page 14: Cancer and Ayurveda

It includes following things,It includes following things,

wake up at Bramha muharta wake up at Bramha muharta danthadhwan danthadhwan anjanavidhi anjanavidhi abhyanga abhyanga vyayamavyayamaudavartanaudavartanasnana vidhisnana vidhi

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Page 15: Cancer and Ayurveda

AaharvidhiAaharvidhi  

cha.su.5/3cha.su.5/3According to Ayurveda diet plays an important role in According to Ayurveda diet plays an important role in manifestation of diease. manifestation of diease. 

cha.sutra.29/45cha.sutra.29/45 Again charka says that , Again charka says that ,

cha.chikista1/2-cha.chikista1/2-33So by following the rules of Aharvidhi we can avoid the So by following the rules of Aharvidhi we can avoid the occurrence of disease.occurrence of disease.

  

cha. sutra.5/13cha. sutra.5/13http://LearnAyurveda.comhttp://LearnAyurveda.com

Page 16: Cancer and Ayurveda

Don’t suppress Adharniya Vegas (natural Don’t suppress Adharniya Vegas (natural urges) urges) 

cha.sutra.7/3-4cha.sutra.7/3-4because it causes all diseasesbecause it causes all diseases

cha.sutra.7cha.sutra.7

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Page 17: Cancer and Ayurveda

Ayurveda not only think about the body but Ayurveda not only think about the body but also about mind, because mind has great also about mind, because mind has great impact on progression of disease. impact on progression of disease. Adoption of ACHARA RASAYAN told in Adoption of ACHARA RASAYAN told in Ayurveda is helpful in mentaining state of Ayurveda is helpful in mentaining state of mental health.mental health.

Cha.chi.1/4-30-35Cha.chi.1/4-30-35

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Page 18: Cancer and Ayurveda

RitucharyaRitucharya

Ayurveda also gives description about Ayurveda also gives description about seasonal regimen i.e. Ritucharya. Which is seasonal regimen i.e. Ritucharya. Which is helpful for making dosha balancing & helpful for making dosha balancing & physiological optimization in all seasons.physiological optimization in all seasons.

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Page 19: Cancer and Ayurveda

ROLE OF PRANAYAMA & YOGAROLE OF PRANAYAMA & YOGA

It helps in mental & emotional It helps in mental & emotional purification. Healing begins with mind so purification. Healing begins with mind so meditation, pranayama, yoga all help to meditation, pranayama, yoga all help to free the blocked mental energy & free the blocked mental energy & promote healing.promote healing.

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Page 20: Cancer and Ayurveda

ROLE OF PANCHAKARMA IN ROLE OF PANCHAKARMA IN PREVENTION OF CANCERPREVENTION OF CANCER

Panchakarma is considered as complete Panchakarma is considered as complete approach to the elimination of root cause of the approach to the elimination of root cause of the disease by different deep cleansing methods. disease by different deep cleansing methods.

Imbalance of doshas can be pacified by Imbalance of doshas can be pacified by Shamana therapies but deep rooted doshas can Shamana therapies but deep rooted doshas can be completely eliminated by Shodhana be completely eliminated by Shodhana procedures such as Panchakarmaprocedures such as Panchakarma..

1.Vamana1.Vamana2.Virechana2.Virechana3.Basti3.Basti4.Nasya4.Nasya5.Raktamokshan5.Raktamokshan

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Page 21: Cancer and Ayurveda

RasayanaRasayana

The use of antioxidants during chemotherapy enhances The use of antioxidants during chemotherapy enhances therapy by reducing the generation of oxidative stress therapy by reducing the generation of oxidative stress induced aldehydes. Natural drugs which are used as induced aldehydes. Natural drugs which are used as Rasayana have been proved earlier to have antioxidant Rasayana have been proved earlier to have antioxidant activities.activities.

There are several evidences which shows effects of There are several evidences which shows effects of Rasayana plants on biomarkers in terms of apoptosis, Rasayana plants on biomarkers in terms of apoptosis, cytroprotection, cell recovery, anti-neo-plastic activity cytroprotection, cell recovery, anti-neo-plastic activity and immune augmentation.and immune augmentation.

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Page 22: Cancer and Ayurveda

Ayurveda can be very useful in both ways i.e. Ayurveda can be very useful in both ways i.e. ““Add years to life and Add life to years.”Add years to life and Add life to years.”

Hundreds of herbal and traditional Hundreds of herbal and traditional compounds are being screened world wide compounds are being screened world wide to validate their use as anti cancerous drug.to validate their use as anti cancerous drug.

Some ayurvedic anti cancerous drugs are as Some ayurvedic anti cancerous drugs are as followsfollows

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Page 23: Cancer and Ayurveda

Tinospora cordifoliaTinospora cordifoliaIt enhances host immune system by increasing It enhances host immune system by increasing immunoglobulin and blood leucocyte by the stimulation immunoglobulin and blood leucocyte by the stimulation of stem cell proliferation of stem cell proliferation

   Piper longumPiper longum

Active alcolide extracted from this plant has anti-Active alcolide extracted from this plant has anti-oxidative potency in both in vitro and in vivo condition oxidative potency in both in vitro and in vivo condition

   Curcuma longa (Turmeric)Curcuma longa (Turmeric)

Curcumin is said to inhibit tumour promoting enzymes Curcumin is said to inhibit tumour promoting enzymes and interfear with the growth of cancerous tumor as a and interfear with the growth of cancerous tumor as a powerful antioxidant it neutralizes free radicals that powerful antioxidant it neutralizes free radicals that increase the risk of cancer.increase the risk of cancer.

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Page 24: Cancer and Ayurveda

AshwagandhaAshwagandha Withania somnifera Immunomodulator Withania somnifera Immunomodulator ChitrakaChitraka Plumbago zeylanicum Anti-tumor Plumbago zeylanicum Anti-tumor ShireeshShireesh Albizzia lebbeck Vishghna Albizzia lebbeck Vishghna ShallakiShallaki Boswellia serrata Vednasthapan Boswellia serrata Vednasthapan MadhuyashtiMadhuyashti Glycirrhizza glabra Daha-shamak Glycirrhizza glabra Daha-shamak PippaliPippali Piper longum Radioprotective Piper longum Radioprotective TulsiTulsi Ocimum sanctum Ocimum sanctum

ChemopreventiveChemopreventive SadabaharSadabahar Vinca rosea Anti-cancer Vinca rosea Anti-cancer HoneyHoney Mel depuratum Mel depuratum GoghritGoghrit Clarified butter Clarified butter GodugdhaGodugdha Milk – good sourceMilk – good source

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Page 25: Cancer and Ayurveda

Rasayana - ApplicationsRasayana - Applications As adjuvant or co-therapy along with chemotherapy or radio-As adjuvant or co-therapy along with chemotherapy or radio-

therapy and post surgery care:therapy and post surgery care: To minimize the side effects of these therapiesTo minimize the side effects of these therapies In reducing the therapeutic dose of various drugs used.In reducing the therapeutic dose of various drugs used. Can be helpful in targeting the specific tissues as in some Can be helpful in targeting the specific tissues as in some

studies on nano-particles of gold.studies on nano-particles of gold. To slower the progress of cancer, when chemotherapy, To slower the progress of cancer, when chemotherapy,

radiotherapy or surgery is contraindicated due to many reasons radiotherapy or surgery is contraindicated due to many reasons and patients have no other choiceand patients have no other choice

With anti-tumor action with the help of herbal / herbo mineral With anti-tumor action with the help of herbal / herbo mineral compounds found to be effective in some studies.compounds found to be effective in some studies.

Cell protective activity of drugs prescribed in Rasayana therapy; Cell protective activity of drugs prescribed in Rasayana therapy; to improve comfort and quality of life for individuals with cancer.to improve comfort and quality of life for individuals with cancer.

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Page 26: Cancer and Ayurveda

ANTITUMOR POTENTIAL OF SOME MEDICINAL ANTITUMOR POTENTIAL OF SOME MEDICINAL

PLANTS BY MODULATING APOPTOSISPLANTS BY MODULATING APOPTOSIS

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Page 27: Cancer and Ayurveda

Questions?Questions?

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Page 28: Cancer and Ayurveda

• Role of apoptosis in cancerRole of apoptosis in cancer

• Apoptotic activity of chemotherapy, radiation and Apoptotic activity of chemotherapy, radiation and

plant based bioactives.plant based bioactives.

• Cytotoxic drugs from plantsCytotoxic drugs from plants

Vinblastine, vincristine - Vinblastine, vincristine - Catharanthus roseus Catharanthus roseus

(Apocynaceae)(Apocynaceae)

Etoposide, teniposide - Etoposide, teniposide - Podophyllum peltatumPodophyllum peltatum, , P. P.

emodi emodi (Berberidaceae)(Berberidaceae)http://LearnAyurveda.comhttp://LearnAyurveda.com

Page 29: Cancer and Ayurveda

Triphala inhibits both Triphala inhibits both in vitro in vitro and and in vivo in vivo xenograft growth of xenograft growth of pancreatic tumor cells by pancreatic tumor cells by

inducing apoptosis - inducing apoptosis - Yan Shi, Ravi P Yan Shi, Ravi P Sahu and Sanjay K SrivastavaSahu and Sanjay K Srivastava

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Page 30: Cancer and Ayurveda

TriphalaTriphala Most commonly used Indian Ayurvedic herbal formulation.Most commonly used Indian Ayurvedic herbal formulation. Consisted of three equal parts of medicinal dried fruitsConsisted of three equal parts of medicinal dried fruits Major ingredients shown to be gallic acid and ascorbic acid.Major ingredients shown to be gallic acid and ascorbic acid. Medicine is rich in natural antioxidants and is believed to promote immunity, Medicine is rich in natural antioxidants and is believed to promote immunity,

health and longevityhealth and longevity A great deal of research is being conducted in India to pursue an A great deal of research is being conducted in India to pursue an

understanding of the underlying biochemical mechanisms associated with understanding of the underlying biochemical mechanisms associated with Triphala of which they are currently unknownTriphala of which they are currently unknown

Triphala significantly reduced benzo(a)pyrene-induced forestomach Triphala significantly reduced benzo(a)pyrene-induced forestomach tumorigenesis in micetumorigenesis in mice

Suppress the growth of MCF-7 breast cancer cells and protect against Suppress the growth of MCF-7 breast cancer cells and protect against radiation oxidative-induced damage.radiation oxidative-induced damage.

Has been shown to provide enhanced cytotoxic effects on cancer cell lines Has been shown to provide enhanced cytotoxic effects on cancer cell lines in vitroin vitro

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Page 31: Cancer and Ayurveda

The effects of Triphala on The effects of Triphala on the survival of human the survival of human

pancreatic cells.pancreatic cells.

• Capan-2 Cells: Human pancreatic cancer cells that express wild-type p53

• PARP (poly-ADP-ribose-polymerase): mediates repair of single strand breaks of DNA via activation and recruitment of DNA repair enzymes

Triphala induces apoptosis in human pancreatic cancer cells with an IC50 of 50µg/mL

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Page 32: Cancer and Ayurveda

Triphala causes DNA damage resulting in Triphala causes DNA damage resulting in activation of p53 in Capan-2 cellsactivation of p53 in Capan-2 cells

Triphala treatment for 24 h led to Triphala treatment for 24 h led to phosphorylation of H2A.X at Ser-phosphorylation of H2A.X at Ser-139 suggesting the presence of 139 suggesting the presence of DNA ds breaks.DNA ds breaks.

DNA damage leads to activation DNA damage leads to activation of p53 by ATM Kinaseof p53 by ATM Kinase

1 h treatment showed sig. 1 h treatment showed sig. upregulation of p53 as well as upregulation of p53 as well as downstream component p21.downstream component p21.

Cells treated with pifithrin-Cells treated with pifithrin- α α, a , a p53 inhibitor, showed inhibition p53 inhibitor, showed inhibition of activation following treatment of activation following treatment with TPL.with TPL.

Pifithrin-Pifithrin- α α also blocked PARP also blocked PARP cleavage in the presence of TPL.cleavage in the presence of TPL.

Suggests TPL provokes an activation of p53 pathway

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Page 33: Cancer and Ayurveda

Activation of ERK Activation of ERK by Triphalaby Triphala

ERK: Part of the MAPK ERK: Part of the MAPK pathwaypathway

Elk: A downstream Elk: A downstream substrate of ERKsubstrate of ERK

MEK: An upstream MEK: An upstream regulator of ERKregulator of ERK

U0126: An inhibitor of U0126: An inhibitor of MEKMEK

Triphala-induced apoptosis is mediated by ERK. ERK may be an upstream regulator of p53 in this system.

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Page 34: Cancer and Ayurveda

Triphala-induced ROS generation triggers Triphala-induced ROS generation triggers ERK activation and apoptosis in Capan-2 ERK activation and apoptosis in Capan-2

cellscells Treatment of Capan-Treatment of Capan-2 cells with 60 ug/ml 2 cells with 60 ug/ml showed increased showed increased ROS generation in ½ ROS generation in ½ hh

Treatment with Treatment with antioxidant N-Acetyl antioxidant N-Acetyl Cysteine (NAC) Cysteine (NAC) inhibited activation of inhibited activation of ERK.ERK.

NAC inhibits induced NAC inhibits induced cell apoptosis due to cell apoptosis due to lack of histone-lack of histone-associated DNA associated DNA fragments in the fragments in the presence of TPL.presence of TPL.

Suggests Triphala mediated ROS is responsible for activation of ERK and/or p53 in induced cell apoptosis

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Page 35: Cancer and Ayurveda

The effect of The effect of Triphala is not cell Triphala is not cell

specificspecific

BxPC-3: Human BxPC-3: Human pancreatic cancer cell pancreatic cancer cell line that express line that express mutated p53.mutated p53.

HPDE-6: Normal HPDE-6: Normal human pancreatic human pancreatic ductal epithelial cellsductal epithelial cells

Treatment of BxPC-C cells with Triphala showed a reduced survival rate with an IC50 of 85µg/mL. However Triphala failed to induce apoptosis in non-cancerous cells.

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Page 36: Cancer and Ayurveda

Triphala inhibits the growth of Capan-2 human Triphala inhibits the growth of Capan-2 human pancreatic xenografts pancreatic xenografts in vivoin vivo

Pancreatic tumor cells were Pancreatic tumor cells were implanted in nude mice implanted in nude mice through subcutaneous through subcutaneous injection followed by oral injection followed by oral uptake of Phosphate buffered uptake of Phosphate buffered saline(PBS) saline(PBS) oror TPL. TPL.

Both TPL group showed Both TPL group showed significantly decreased tumor significantly decreased tumor volume sizevolume size

TUNEL assay showed TUNEL assay showed increased number of apoptotic increased number of apoptotic cell bodies in TPL groups.cell bodies in TPL groups.

Cleavaged PARP and Cleavaged PARP and caspase-3 components were caspase-3 components were shown in Western blot shown in Western blot analysis of TPL treated analysis of TPL treated groups.groups.

TPL plays a role in activation of induced apoptosis of cancerous pancreatic xenografts

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Summary and Conclusions for study on TriphalaSummary and Conclusions for study on Triphala

Triphala treatment reduces the survival rate of human pancreatic cancer Triphala treatment reduces the survival rate of human pancreatic cancer cells in vitro, but failed to cause cytotoxic effects on non-cancerous cells.cells in vitro, but failed to cause cytotoxic effects on non-cancerous cells.

Triphala induced apoptosis in Capan-2 cells was associated to the Triphala induced apoptosis in Capan-2 cells was associated to the generation of reactive oxygen species.generation of reactive oxygen species.

The generation of reactive oxygen species caused DNA damage resulting in The generation of reactive oxygen species caused DNA damage resulting in the activation of ATM and ERK which lead to the stabilization of p53.the activation of ATM and ERK which lead to the stabilization of p53.

By introducing U0126, MEK and therefore ERK was inhibited; and Pifithrin-By introducing U0126, MEK and therefore ERK was inhibited; and Pifithrin-αα inhibited p53 activity in Capan-2 cell. inhibited p53 activity in Capan-2 cell.

U0126 treatment also blocked apoptosis in Triphala treated BxPC-3 cells U0126 treatment also blocked apoptosis in Triphala treated BxPC-3 cells as well. This suggested that ERK was a molecular target of Triphala in as well. This suggested that ERK was a molecular target of Triphala in pancreatic cancer cells.pancreatic cancer cells.

Triphala caused reduced tumor growth in vivo. Mice with Capan-2 Triphala caused reduced tumor growth in vivo. Mice with Capan-2 xenografts were treated with Triphala every 5 days orally.xenografts were treated with Triphala every 5 days orally.

Increased apoptosis of these tumor cells in mice was observed, and was Increased apoptosis of these tumor cells in mice was observed, and was due to the activation of ERK and p53.due to the activation of ERK and p53.

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Page 38: Cancer and Ayurveda

Other plants having apoptosis Other plants having apoptosis capacity capacity

Paclitaxel, docetaxel - Taxus brevifolia Paclitaxel, docetaxel - Taxus brevifolia

(Taxaceae)(Taxaceae) Irinotecan, topotecan, 9-aminocampothecin, Irinotecan, topotecan, 9-aminocampothecin, 9 - nitrocamptothecin. Camptotheca acuminate 9 - nitrocamptothecin. Camptotheca acuminate

(Nyssaceae). (Nyssaceae). Homoharringtonine - Harringtonia Homoharringtonine - Harringtonia

cephalotaxus (Cephalotaxaceae)cephalotaxus (Cephalotaxaceae) 4-Ipomeanol - Ipomoeca batatas (Convolvulaceae)4-Ipomeanol - Ipomoeca batatas (Convolvulaceae) Elliptinium - Bleekeria vitensis (Apocynaceae)Elliptinium - Bleekeria vitensis (Apocynaceae)

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Page 39: Cancer and Ayurveda

Flavopiridol - Flavopiridol - Amoora rohitukaAmoora rohituka; ; Dysoxylum Dysoxylum binectariferum binectariferum (Maliaceae).(Maliaceae).

• Camptothecin Camptothecin 88, Paclitaxil , Paclitaxil 99 and Taxol and Taxol 1010

and their apoptotic activity in cancer.and their apoptotic activity in cancer.• Tylophora alkaloids induced apoptosis in Tylophora alkaloids induced apoptosis in

K562 cells (Human erythroleukemic cell K562 cells (Human erythroleukemic cell line) line) 1111..

• Gingerol, oleoresin from rhizomes of Gingerol, oleoresin from rhizomes of Ginger induced apoptosis in cultured HL-Ginger induced apoptosis in cultured HL-60 cells 60 cells 1212..

• Terminalia chebula - fruit Terminalia chebula - fruit 13.13.. . http://LearnAyurveda.comhttp://LearnAyurveda.com

Page 40: Cancer and Ayurveda

Acutiaporberine, derivative from Thalicrum Acutiaporberine, derivative from Thalicrum acutifolium induced apoptosis in human lung cancer acutifolium induced apoptosis in human lung cancer cell-line 95-D.cell-line 95-D.

Curcumin induced Curcumin induced in AK - 5 tumor cell lines (a rat histiocytoma), S180, in AK - 5 tumor cell lines (a rat histiocytoma), S180,

HT-29, HL60, NIH 3T3 cell lines HT-29, HL60, NIH 3T3 cell lines ; induced apoptosis ; induced apoptosis in CA46 cells (human Burkitt`s lymphoma cell line).in CA46 cells (human Burkitt`s lymphoma cell line).

Liquorice root extract induced apoptosis, G2/M cell Liquorice root extract induced apoptosis, G2/M cell cycle arrest in breast and prostate tumor cells.cycle arrest in breast and prostate tumor cells.

Amooranin, isolated from the stem bark of Indian Amooranin, isolated from the stem bark of Indian tree (Amoora rohituka), induced apoptosis in human tree (Amoora rohituka), induced apoptosis in human mammary carcinoma MCF-7, multidrug resistant mammary carcinoma MCF-7, multidrug resistant breast carcinoma MCF-7/TH and breast epithelial breast carcinoma MCF-7/TH and breast epithelial MCF-10A cell lines.MCF-10A cell lines.

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Resveratrol (Res) derivatives, which were Resveratrol (Res) derivatives, which were isolated from stem bark of Vatica rassak isolated from stem bark of Vatica rassak (Dipterocarpaceae), were evaluated for in (Dipterocarpaceae), were evaluated for in vitro cytotoxicity against a panel of human vitro cytotoxicity against a panel of human tumor cell lines. Vaticanol C (Vat C) tumor cell lines. Vaticanol C (Vat C) induced a considerable cytotoxicity in all induced a considerable cytotoxicity in all cell lines tested and exhibited growth cell lines tested and exhibited growth suppression in colon cancer cell lines at suppression in colon cancer cell lines at low doselow dose1818: resveratrol induced apoptosis : resveratrol induced apoptosis in HL60 human leukemia cell-line in HL60 human leukemia cell-line 3030, , T47D breast carcinoma cell lines T47D breast carcinoma cell lines 2424..

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Phyllanthus urinaria extract – induced Phyllanthus urinaria extract – induced apoptosis in Lewis lung carcinoma cells.apoptosis in Lewis lung carcinoma cells.

Aqueous fraction of Withania somnifera, Aqueous fraction of Withania somnifera, induced apoptosis in mouse skeletal induced apoptosis in mouse skeletal muscle cell line C2C12. muscle cell line C2C12.

• Uncaria tomentosa has shown Uncaria tomentosa has shown antiproliferative effects on human leukemic antiproliferative effects on human leukemic Cell-lines (HL60) and human EBV - Cell-lines (HL60) and human EBV - transformed B lymphoma cell line (Raji) by transformed B lymphoma cell line (Raji) by induction of apoptosis.induction of apoptosis.

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Crocus sativus (Saffron), Panax ginseng, Crocus sativus (Saffron), Panax ginseng, Tinospora cordifolia and Emblica officinalis Tinospora cordifolia and Emblica officinalis showed their apoptotic inducting property in showed their apoptotic inducting property in various experiments .various experiments .

Viscum album induced apoptosis in cultured Viscum album induced apoptosis in cultured human lymphocytes human lymphocytes 2424,,2727

Methanolic extract of Digitalis purpurea subsp Methanolic extract of Digitalis purpurea subsp heywoodii has been assessed for cytotoxic heywoodii has been assessed for cytotoxic activity against three human cancer cell lines, activity against three human cancer cell lines, using the SRB assay. Morphological apoptosis using the SRB assay. Morphological apoptosis evaluation of the Methanolic extract on the TK-10 evaluation of the Methanolic extract on the TK-10 cell line showed that its cytotoxicity was mediated cell line showed that its cytotoxicity was mediated by an apoptotic effect by an apoptotic effect 2828..

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Pycnogenol, a mixture of flavonoid compounds Pycnogenol, a mixture of flavonoid compounds extracted from the bark of pine trees selectively extracted from the bark of pine trees selectively induced death in human mammary cancer cells induced death in human mammary cancer cells (MCF-7) and not in normal human mammary MCF-(MCF-7) and not in normal human mammary MCF-10 cells .10 cells .

Extracts from Solanum muricatum (CSG) inhibited Extracts from Solanum muricatum (CSG) inhibited tumor growth both in vivo and in vitro by inducing tumor growth both in vivo and in vitro by inducing apoptosis in prostate (PC3, DU145), stomach apoptosis in prostate (PC3, DU145), stomach (MKN45), liver (QGY-7721, SK-HEP-1), breast (MKN45), liver (QGY-7721, SK-HEP-1), breast (MDA-MB-435), ovarian (OVCAR), colon (HT29) (MDA-MB-435), ovarian (OVCAR), colon (HT29) and lung (NCI-H209) cancer cells; NHP (prostate), and lung (NCI-H209) cancer cells; NHP (prostate), HUVEC (umbilical vein endothelial cell), and WI-38 HUVEC (umbilical vein endothelial cell), and WI-38 (lung diploid fibroblasts) normal cells .(lung diploid fibroblasts) normal cells .

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• Tanshinone II - A, isolated from Salvia Tanshinone II - A, isolated from Salvia miltiorrhiza BUNGE induced apoptosis in miltiorrhiza BUNGE induced apoptosis in human leukemia cell lines (HL60 and human leukemia cell lines (HL60 and K562) through the activation of caspase – K562) through the activation of caspase – 3 . 3 .

• Styrylpyrone derivative (SPD) is a Styrylpyrone derivative (SPD) is a pharmacologically active compound pharmacologically active compound extracted from the plant extracted from the plant Goniothalamus Goniothalamus spsp. of the Annonaceae family . SPD as a . of the Annonaceae family . SPD as a potent antiproliferative agent on MCF-7 potent antiproliferative agent on MCF-7 cells by inducing apoptosis in a caspase-cells by inducing apoptosis in a caspase-7-dependent manner .7-dependent manner .

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• It has been estimated that only 5 -15% of It has been estimated that only 5 -15% of the approximately 250 000 species of the approximately 250 000 species of higher plants have been systematically higher plants have been systematically investigated for the presence of bioactive investigated for the presence of bioactive compounds. Hence a lot of untapped compounds. Hence a lot of untapped potential is left in plants. potential is left in plants.

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REFERENCESREFERENCES How apoptosis is regulated, and what goes wrong in How apoptosis is regulated, and what goes wrong in

cancer: Johanna Sjöström and Jonas Bergh.  BMJ 2001; cancer: Johanna Sjöström and Jonas Bergh.  BMJ 2001; 322:1538-1539 (23 June).322:1538-1539 (23 June).

What is apoptosis and why is it important: Andrew What is apoptosis and why is it important: Andrew G Renehan, Catherine Booth and Christopher S Potten; G Renehan, Catherine Booth and Christopher S Potten; BMJ 2001; 322:1536-1538 (23 June).  BMJ 2001; 322:1536-1538 (23 June). 

Apoptosis: a basic biological phenomenon with wide-Apoptosis: a basic biological phenomenon with wide-ranging implications in tissue kinetics, Kerr JFR, Wyllie AH, ranging implications in tissue kinetics, Kerr JFR, Wyllie AH, Currie AR:Currie AR: Br J Cancer 1972, 26Br J Cancer 1972, 26::239 - 257.239 - 257.

To die or not to die: An overview of apoptosis and its role in To die or not to die: An overview of apoptosis and its role in disease,disease, Hetts SW: JAMA 1998, 279(4):300-307.Hetts SW: JAMA 1998, 279(4):300-307.

Disruption of p53 function in immortalized human cells does Disruption of p53 function in immortalized human cells does not affect survival or apoptosis after Taxol or Vincristine not affect survival or apoptosis after Taxol or Vincristine treatment,treatment, Fan S, Cherney B, Reinhold W, Rucker K, Fan S, Cherney B, Reinhold W, Rucker K, O’Connor PM: Clinical Cancer Research 1998, 4O’Connor PM: Clinical Cancer Research 1998, 4::1047-1047-1054.1054.

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Apoptosis and the Dilemma of Cancer Chemotherapy, Hannun Apoptosis and the Dilemma of Cancer Chemotherapy, Hannun AYAY. . Blood 1997, 89Blood 1997, 89::1845-1853.1845-1853.

Anti-Cancer Drug Discovery and Development in Brazil: Targeted Anti-Cancer Drug Discovery and Development in Brazil: Targeted Plant Collection as a Rational Strategy to Acquire Candidate Anti Plant Collection as a Rational Strategy to Acquire Candidate Anti - Cancer Compounds Dennis .A. mans, Adriana B. Da rocha, - Cancer Compounds Dennis .A. mans, Adriana B. Da rocha, Gilberto Schwartsmann. The OncologistGilberto Schwartsmann. The Oncologist 2000; 5:185 – 198.2000; 5:185 – 198.

Apoptotic response to Camptothecin and 7- ydroxystaurosporine Apoptotic response to Camptothecin and 7- ydroxystaurosporine (UCN-01) in the human breast cancer cell lines of the NCI (UCN-01) in the human breast cancer cell lines of the NCI Anticancer Drug Screen: multifactorial relationships with Anticancer Drug Screen: multifactorial relationships with topoisomerase I, Protein Kinase C, Bcl-2, p53, MDM-2 and topoisomerase I, Protein Kinase C, Bcl-2, p53, MDM-2 and caspase pathways: Nieves-Neira W, Pommier Y, Int J Cancer. caspase pathways: Nieves-Neira W, Pommier Y, Int J Cancer. 1999 Jul 30; 82(3):396-404.1999 Jul 30; 82(3):396-404.

Paclitaxel-induced apoptosis in non-small cell lung cancer cell Paclitaxel-induced apoptosis in non-small cell lung cancer cell lines is lines is associated with increased caspase-3 activity: Weigel TL et al:J associated with increased caspase-3 activity: Weigel TL et al:J Thorac Cardiovasc Surg. 2000 Apr;119(4 Pt 1):795-803.Thorac Cardiovasc Surg. 2000 Apr;119(4 Pt 1):795-803.

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Taxol-induced apoptosis in human SKOV3 ovarian and MCF7 Taxol-induced apoptosis in human SKOV3 ovarian and MCF7 breast carcinoma cells is caspase-3 and caspase-9 independent. breast carcinoma cells is caspase-3 and caspase-9 independent. Ofir R, Seidman R, Rabinski T, Krup M, Yavelsky V, Weinstein Y, Ofir R, Seidman R, Rabinski T, Krup M, Yavelsky V, Weinstein Y, Wolfson M., Cell Death Differ. 2002 Jun; 9(6):636-42.Wolfson M., Cell Death Differ. 2002 Jun; 9(6):636-42.

Induction of apoptosis in a human erythroleukemic cell line K562 Induction of apoptosis in a human erythroleukemic cell line K562 by Tylophora alkaloids involves release of Cytochrome c and by Tylophora alkaloids involves release of Cytochrome c and activation of Caspase 3: Ganguly T, Khar A: Phytomedicine 2002 activation of Caspase 3: Ganguly T, Khar A: Phytomedicine 2002 May; 9(4):288-95.May; 9(4):288-95.

Antitumor promoting potential of selected spice ingredients with Antitumor promoting potential of selected spice ingredients with antioxidative and anti-inflammatory activities: Young-Joon Surh; antioxidative and anti-inflammatory activities: Young-Joon Surh; Food and Chemical Toxicology 40(2002), 1091-7.Food and Chemical Toxicology 40(2002), 1091-7.

Inhibition of Cancer cell growth by crude extract and the Inhibition of Cancer cell growth by crude extract and the phenolics of Terminalia chebula retz fruit: Journal of phenolics of Terminalia chebula retz fruit: Journal of ethanopharmacology 81(3), 2002, 327-336. ethanopharmacology 81(3), 2002, 327-336.

Apoptosis of human highly metastatic lung cancer-line 95-D Apoptosis of human highly metastatic lung cancer-line 95-D induced by Acutiaporberine, a novel bisalkaloid from Thalicrum induced by Acutiaporberine, a novel bisalkaloid from Thalicrum acutifolium: Planta medica 68(6), 2002, 550-553.acutifolium: Planta medica 68(6), 2002, 550-553.

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Curcumin mediated apoptosis in AK-5 tumor cells involves the Curcumin mediated apoptosis in AK-5 tumor cells involves the production of reactive oxygen intermediates: Bhaumik S et al, production of reactive oxygen intermediates: Bhaumik S et al, FEBS Lett 1999 Aug 6; 456(2):311-4.FEBS Lett 1999 Aug 6; 456(2):311-4.

Novel polyphenol molecule isolated from Licorice root induces Novel polyphenol molecule isolated from Licorice root induces apoptosis, G2/M cell cycle arrest and Bcl-2 phosphorylation in apoptosis, G2/M cell cycle arrest and Bcl-2 phosphorylation in tumor cell lines: Rafi MM et al, J Agri Food Chem 2002 Feb 13; tumor cell lines: Rafi MM et al, J Agri Food Chem 2002 Feb 13; 50(4):677-84.50(4):677-84.

Novel drug Amooranin induces apoptosis through caspase Novel drug Amooranin induces apoptosis through caspase activity in human breast carcinoma cell lines: Rabi T, activity in human breast carcinoma cell lines: Rabi T, Ramachandran C, Fonseca HB, Nair RP, Alamo A, Melnick SJ, Ramachandran C, Fonseca HB, Nair RP, Alamo A, Melnick SJ, Escalon E. Breast Cancer Res Treat. 2003 Aug; 80(3):321-30. Escalon E. Breast Cancer Res Treat. 2003 Aug; 80(3):321-30.

Antitumor effect of resveratrol oligomers against human cancer Antitumor effect of resveratrol oligomers against human cancer cell lines and the molecular mechanism of apoptosis induced cell lines and the molecular mechanism of apoptosis induced by Vaticanol C: Ito T, Akao Y, Yi H, Ohguchi K, Matsumoto K, by Vaticanol C: Ito T, Akao Y, Yi H, Ohguchi K, Matsumoto K, Tanaka T, Iinuma M, Nozawa Y, Carcinogenesis. 2003 Sep; Tanaka T, Iinuma M, Nozawa Y, Carcinogenesis. 2003 Sep; 24(9):1489-97. Epub 2003 Jul 04.24(9):1489-97. Epub 2003 Jul 04.

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Phyllanthus urinaria triggers the apoptosis and Bcl-2 down-Phyllanthus urinaria triggers the apoptosis and Bcl-2 down-regulation in Lewis lung carcinoma cells : Huang ST, Yang regulation in Lewis lung carcinoma cells : Huang ST, Yang RC, Yang LJ, Lee PN, Pang JH, Life Sci. 2003 Feb RC, Yang LJ, Lee PN, Pang JH, Life Sci. 2003 Feb 28;72(15):1705-16. 28;72(15):1705-16.

Silymarin Suppresses TNF-Induced Activation of NF-B, c-Jun Silymarin Suppresses TNF-Induced Activation of NF-B, c-Jun N- Terminal Kinase, and Apoptosis: Sunil K. Manna, Asok N- Terminal Kinase, and Apoptosis: Sunil K. Manna, Asok Mukhopadhyay, Nguyen T. Van and Bharat B. Aggarwal: The Mukhopadhyay, Nguyen T. Van and Bharat B. Aggarwal: The Journal of Immunology, 1999, 163: 6800-6809. Journal of Immunology, 1999, 163: 6800-6809.

Down regulation of p34cdc2 expression with aqueous fraction Down regulation of p34cdc2 expression with aqueous fraction from Withania somnifera for a possible molecular mechanism from Withania somnifera for a possible molecular mechanism of anti-tumor and other pharmacological effects: D Singh, C S of anti-tumor and other pharmacological effects: D Singh, C S Payal and K K Bhutani, Phytomedicine 8(6), 492-94.Payal and K K Bhutani, Phytomedicine 8(6), 492-94.

Modulation of programmed cell-death by medicinal plants: Modulation of programmed cell-death by medicinal plants: Urmila thatte, Seema bagadey and Sharadini dahanukar, Urmila thatte, Seema bagadey and Sharadini dahanukar, Cellular and Molecular Biology 46(1), 199-214.Cellular and Molecular Biology 46(1), 199-214.

Anticancer activities of Curcumin on human Burkitt`s Anticancer activities of Curcumin on human Burkitt`s lymphoma: Wu Y et al, Zhonghua Zhong Liu Za Zhi 2002 Jul: lymphoma: Wu Y et al, Zhonghua Zhong Liu Za Zhi 2002 Jul: 24(4): 348-52.24(4): 348-52.

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An overview on anticancer activities of the An overview on anticancer activities of the Viscum album extractViscum album extract Isorel: Isorel: Zarkovic N et al, et al, Cancer Biother Radiopharm 2001 Feb 16:55-62. Cancer Biother Radiopharm 2001 Feb 16:55-62.

Anti-tumor activity of Digitalis purpurea L. subsp. Anti-tumor activity of Digitalis purpurea L. subsp. heywoodii: Lopez-Lazaro M et al; Planta Med. heywoodii: Lopez-Lazaro M et al; Planta Med. 2003 Aug; 69(8):701-4.2003 Aug; 69(8):701-4.

Synthesis and biological evaluation of Synthesis and biological evaluation of resveratrol and analogues as apoptosis-resveratrol and analogues as apoptosis-inducing agents: Roberti M, et al; J Med Chem. inducing agents: Roberti M, et al; J Med Chem. 2003 Jul 31;46(16):3546-54.2003 Jul 31;46(16):3546-54.

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The world wide exploration of nature for The world wide exploration of nature for novel anticancer agents, Cragg G M, D.J. novel anticancer agents, Cragg G M, D.J. Newman, R.B.Weiss: Coral reefs, forests Newman, R.B.Weiss: Coral reefs, forests and thermal vents: – seminar in oncology, and thermal vents: – seminar in oncology, 24 1997, 156-163. 24 1997, 156-163.

Discovery and development of Discovery and development of antineoplastic agents from natural antineoplastic agents from natural agents from natural sources, Cragg G.M., agents from natural sources, Cragg G.M., D.J.Phil: Cancer invest, 17, 1999, 153-163. D.J.Phil: Cancer invest, 17, 1999, 153-163.

Apoptosis in Cancer: Lowe SW, Lin AW:Apoptosis in Cancer: Lowe SW, Lin AW: Carcinogenesis 2000, 21(3)Carcinogenesis 2000, 21(3): : 485 - 95485 - 95..

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