international journal of innovative pharmaceutical...

REVIEW ARTICLE Rita Kundu et.al / IJIPSR / 3 (2), 2015, 72-89

Department of Botany ISSN (online) 2347-2154

Available online: www.ijipsr.com February Issue 72

ANTI-CANCEROUS AND ANTI-TUMOROUS ACTIVITY OF

ALGAE –A REVIEW

1Indira Majumder,

2Subhabrata Paul,

3Rita Kundu

*

Centre of Advanced Study, Department of Botany, University of Calcutta, INDIA

Corresponding Author

Rita Kundu

Department of Botany,

Centre of Advanced Study, Department of Botany,

University of Calcutta, INDIA

Email: [email protected]

International Journal of Innovative

Pharmaceutical Sciences and Research www.ijipsr.com

Abstract

Cancer is a multigenic disease causing about one fifth of the deaths in each year worldwide. Cancer is

caused mainly due to mutation or malfunction of cell cycle controlling machineries. Standard treatment for

curing cancer including chemotherapies, coupled with radiation therapies are available but sometime they

are associated with severe side effects , as for example, radiation therapies partially disrupts patient’s

normal immune systems. Nausea, vomiting, loss of appetite are also common side effects of those standard

treatment. Complementary and alternative medicines or CAM treatments opened up a new pathway which

relies on active botanicals obtained from various plant sources. CAM obtained from marine flora specially

from both micro- and macro algae reported to have active anticarcinogenic potentiality. Marine algae

constitute about 90% of marine organisms diversity, at the same time contain diverse types of

biomolecules; such as vitamins, minerals, dietary fibres, sterol, polyphenols, different types of

polysaccharides and numerous secondary metabolites. These chemical diversity and huge unused biomass

of algae can be explored for drug development. Algal biotdiversity was previously used commercially to

make neutraceuticals, food supplements, meals, gelling substances. Recent research work revealed their

active anticarcinogenic potentiality. Most of the algal extracts induce cancer cell death by inducing

apoptosis or pre-apoptosis either by caspase dependent or caspase independent pathways. In this review, we

have discussed in brief about the antiproliferative properties of some of these algae and their active

anticarcinogenic compounds, belonging to Cyanophyceae,Chlorophyceae,Phaeophyceae and

Rhodophyceae.

Keywords: Cancer, Marine algae, anticarcinogenic.

mailto:[email protected]




INTRODUCTION

Cancer is the leading cause of death in the well-developed as well as developing

countries.According to Globocan14.1 million new cases, and 8.2 million death due to cancer was

reported globally in 2012. Lung, liver, stomach, colorectal and breast cancers cause most cancer

deaths worldwide. In low and middle income countries , 20% of cancer deaths are caused due to

viral infections such as HBV/HCV and HPV infections. It was estimated that annual record of

cancer cases will increase from 14 millon in 2012 to 22 million in the next two decades.This

statistics of cancer cases and mortality rates clearly indicates the great threat of this dreaded

disease.Causes of cancer are multiple,it may be familial, may be due to viral infection ,or may be

related with obesity and life-style patterns.Standard treatments involve many therapies , such as

chemotherapy, surgical therapy, radiation therapy, adjuvant therapies etc.which are associated with

severe side effects.Those side effects include nausea, vomiting, loss of appetite, loss of hair and

impairment of the immune systems by the chemotherapeutic drugs used to stimulate CD34+ cells

and migration of bone marrow stem cell in vivo. Chemotherapeutic drugs sometimes coupled with

radiation or without radiation can damage blood producing cells,resulting in low blood cell count,

increasing the chances of frequent infection, as white blood cell count decreases; severe bleeding

may occur due to decreased platelet count, breathing problems may also increase as red blood cells

are decreasing. Diarrhoea can also result during radiation therapy. At the same time, cancer

treatment by conventional chemotherapy is much expensive and unaffordable for third world

countries.

That’s why, many are opting for an alternative medicine which has lesser/ no side effects, at the

same time affordable to all. According to Natural Cancer Institute (NCI), Maryland, USA;

‘Complementary and alternative medicine (CAM) standard treatments are based on scientific

evidence from research studies’. This includes treatments by using natural products or

“botanicals”. Natural products derived from plants, marine organisms and microorganisms have

drawn attention of many scientists. Some important findings have also gained significance for

natural biomolecules in the field of cancer research. The general acceptance of CAM is good ,

with recent reports stating that 34%–38% of the US adult population are using CAM. The

effective goodness stored in nature and its natural products are yet to be unfolded and can be

explored, most of which till remain in research level.




Algae in both micro and macro form have tremendous scope for exploring bioactive compounds.

They have been used traditionally for medicinal purposes in India, China, Japan, Korea, Ireland,

Wales and other countries. Brown seaweeds (macro algae) are reported to have antinflammatory,

antitumoral and immunostimulant activities [1]. Laminaria, Undaria and some other members of

brown algae are recognized sources of Iodine .Marine algae are sources of pharmacologically

active metabolites [2] having antimicrobial, antineoplastic and antiviral properties.

Marine environment covers about 75% of total Earth’s surface. Marine organism diversity is very

rich and composed of about half of total biodiversity of world. Microalgal and macroalgal flora

comprising 90% of total marine biomass, contain various novel compounds which can be

explored for treating diseases. Soft-bodied marine macroweeds need various types of chemicals to

protect themselves from various adversities. Besides that, numerous microalgae is reported to

contain various essential compounds. These chemical diversity can be explored for potential drug

development. Algae provide many vitamins including: A, B₁,B₂, B6, niacin and vitamin C and

are rich in iodine, potassium, iron, magnesium, and calcium.Polysaccharides, also a major

compound used for food, fodder and therapeutics are also obtained from marine algae

(Rhodophyceae). Poly unsaturated fatty acid (PUFA ) which are precursor of

eicosanoids,regulating normal physiology and body homeostasis are found in many macroalgae

[3]. Seaweeds have different carotenoid pigments , green seaweed species have β-carotene, luetin,

violaxanthin, neoxanthine and zeaxanthine while red seaweeds contain mainly α and β carotene,

luetin and zeaxanthin. In brown seaweeds β-carotene, violanxanthine and fucoxanthine are

present [4]. Algae contain diverse types of sterols, fucosterol , cholesterol and sitosterol are found

in chlorophyceae; brassicasterol, cholesterol, fucosterol are found in phaeophyceae; desmosterol,

sitosterol, cholesterol, fucosterol, chlinasterol etc. are found in rhodophyceae. [5,6].

Fibers found in different algal groups are also diverse, cellulose, mannans and xylan are water

insoluble whereas agars, alginic acid, porphyran, furonan and laminarin are important water

soluble fibers mostly found in sea-weed [7]. These seaweed’s fibers contain some valuable

nutrients as well as pharmacologically active substances, and nowadays there is a lot of interest in

seaweed meal, functional foods and nutraceutical for human consumption. These phytochemical

diversity of macroalgae now a days are being used as alternative food supplement and the algal

compounds are reported to have anti viral, anti bacterial and anti fungal activity. There is a huge

scope to obtain novel bioactive compounds from these unexplored large bio-mass of sea

organisms.




In this present review we have been trying to encompass the beneficial role of marine macro and

micro weeds primarily against uncontrolled cell proliferation and subsequent tumor formation.

Anti-cancerous activity and anti-tumor activity of marine algae:

In the present days alga is not only used as food but also as medicine, as its medicinal value to

treat life-threatening diseases is being explored by researchers worldwide. Biogenic compounds

such as plant extracts from lower groups of unicellular alga to higher groups of plants are used as

complementary therapeutics which has little/no side effects and are safe. Algal extracts are

expected to show anti-cancerous activity and its therapeutic properties can be explored to avoid

the side effects of chemotherapeutic drugs and radiation therapy used to treat various types of

cancer by conventional ways. Some novel bioactive compounds that serve as anti cancerous

compound are derived from algae. Tumor development is associated with escaping normal

cellular cell death process or apoptotic pathways leading towards uncontrolled cell proliferation.

The tumor development starts when a single cell become mutated and proliferates abnormally.

Additional mutation followed by selection of more rapidly growing cells within the population

that results in progression of the tumor and malignancy. Destroying normal cellular homeostasis,

those kinds of cells show variety of biochemical and physiological changes and become resistant

to conventional chemotherapeutics during transformation process.

Many ayurvedic agencies also suggest patients who are suffering from cancer to take

neutraceutical medicines made from algal origin. National cancer institute (NCI,USA), approved

the use of crude extracts from plant origin and pure fractionated extract with IC₅₀ values

≤50µg/ml and ≤4µg/ml .

BLUE-GREEN ALGAE (CYANOPHYCEAE):

They are known as the source of neurotoxins. Along with them other biologically active

molecules are also isolated from them. Cryptophycin 1 isolated from Nostocsp GSV 224 showed

cytoxicity against human tumor cell lines and solid tumors.Cryptophycin strongly suppressed the

ability of microtubules to assemble in vitro. A semi-synthetic analogue Cryptophycin-8 was

found to be more efficient in vivo [8,9]. A boron containing metabolite Borophycin, an acetate

derived polyketide compound, isolated from marine Nostoc linckia and N. spongiaeforme var.

tenue had exhibited potent cytotoxicity against LoVo and KB cell lines [10,11].

Cucarin-A, isolated from Lyngbya majuscula (Curacao collections) is a selective inhibitor of

various cancer ( breast, colon, renal ) cell lines. It acts by inhibiting tubulin polymerization by




binding in the Colchicine binding pocket [12].. Brominated fatty acid from extracts of Anabaena

cylindrica and A. variabilis had shown anti-tumour properties [13]. Several strains of marine

benthic cyanobacteria, Anabaena sp. like M4, 27, 30, 44, 45 have activity against AML cells, but

not against non-malignant cells like hepatocytes and cardiomyoblasts [14]. Yessotoxins isolated

from algal extract Protoceratium reticulatum, was able to induce apoptosis in Hela cells with

clear morphological changes,DNA fragmentation along with changes in mitochondrial membrane

potential [15]. Calothrixins A and B isolated from Calothrix sp. are indole phenanthridine

alkaloids. They have shown cytoxicity against HeLa cells in nanomolar concentrations [16].

Scytonemin isolated from Stigonema sp, previously known natural sunscreen is also found to be

antiproliferative for some human fibroblast and endothelial cells. It acts as serine-threonine kinase

and functions through regulating cell cycle and have role in regulation of mitotic spindle

formation [17]. Leptolyngbya sp. contain a novel n-methyl – depsipeptide coibamide, (synthetic

name:N-{(2S)-2-[(N,N-Dimethyl-L-valyl)oxy]-3-methylbutanoyl}-N,O-dimethyl-L-seryl-N-

[(3S,6S,9S,12S,15S,18S,21S,22R)-15-[(2S)-2-butanyl]-9-isobutyl-6-(4-methoxybenzyl)-18-

(methoxymethyl)-3,4,10,12,16,19,22-heptamethyl-2,5,8,11,14,17,20-heptaoxo-1-oxa-

4,7,10,13,16,19-hexaazacyclodocosan-21-yl]-N,N2-dimethyl-L-leucinamide,formula:

C₆₅H₁₁₀N₁₀O₁₆) that induced autophagosome formation and mTOR independent cell death in

human U87-SG and SF-295 glioblastoma cells and mouse embryonic fibroblasts (MEF) cells.

This natural compound acted differentially in different cell lines. In case of U87-SG cells, it

induced caspase-3 activation while formation of vacuoles was observed in SF-295 cells [18].

Coibamide-A also had displayed potent cytotoxicity against NCI-H460 lung cancer cell line in

nanomolar range. It showed dose dependent increase of G1 cells without interfering with tubulin

and actin. Later this compound was screened against NCI’s panel of 60 cell lines selective for

breast, colon, ovarian cancer cells and found to be most cytotoxic against MDA-MB-231 cell line

(2.8nM). [19].

C-Phycocyanin isolated from Spirulina platensis induced morphological changes along with

DNA fragmentation, increased Fas expression, ICAM expression, decreased Bcl-2 expression and

activation of caspase 2,3,4,6,8,9,10 in HeLa cell line and also showed activity against MCF7 cells

[20]. Ethanolic extracts of Aphanizomenon flos-aquae had arrested AML cell lines at G0-G1

stage[21]. Aphanizomenon flos-aquae & Haematococcus pluvialis were reported to inhibit

proliferation of HL-60 and MV-4-11 cell lines [21]. Treatment with Phormidium molle extracts or

growth media altered mainly the adherent cells (HeLa, Jurkat, U-937, A2058, RD, 3T3,FL)




showing dose-dependent destruction of the monolayer and morphological changes [22]. LU

103793 (N,N dimethyl-i.-valyl-L-valyl-W-methyl-L-valyl-Lprolyl-L-prolinebenzylamide) novel

compound from Symploca sp.also act as an anticarcinogenic and anti tumor agent to interfere with

microtubule synthesis [23]. Largazole isolated from Symploca sp. also act as an potent

anticancerous agent which decreased the level of type 1 histone deacetylase enzyme (HDAC)

[24].

Green algae (chlorophyceae):

Marine filamentous algae Galaxaura marginata was reported to be an anti cancerous alga which

contain a novel desmosterol compound: 25-hydroperoxy-6β-hydroxycholesta-4,23(E)-dien-3-one,

extracted in Ethylacetate; showed cytotoxicity against P338(Lymphocytic leukemia cells), A549

(human lung adenocarcinoma epithelial cell line), KB(KERATIN-forming tumor cell line HeLa)

cell lines with effective doses of 0.28µg/mL, 1.00µg/mL and 0.40µg/mL respectively [25]. Hot

water soluble polysaccharide compound derived from marine chlorophycean algae Capsosiphon

fulvescens, induced apoptotic caspase-3 cascade activation, increased concentration of Bcl-2

regulatory protein and induced cell death in AGS gastric cancer cells via IGF-IR mediated

PI3K/AKT pathway [26]. Dichloromethane: methanol extract from two chlorophycean alga

Udotea flabellum and U. conglutinate with effective concentrations of 22.5 µg/ml and 22.2 µg/ml

showed anti cancerous activities on human cancer cell line HeLa [27]. . Extracts of Udotea

flabellum was reported to have antiproliferative activity on HeLa, SiHa and KB cell lines [27].

Methanolic extracts obtained from two green algae Enteromorpha intestinales and Rhizoclonium

riparium actively showed antiproliferative potentials against cervical cancer cell line HeLa with

IC50 values 309.048 ± 3.083 µg/ml and 506.081 ± 0.714 µg/ml respectively [28]. One green algal

genera Enteromopha prolifera had suppressive activity to Erhlich’s carcinoma with 51.7%

inhibition [29].

Caulerpenyne a sesquiterpene, with a bisenol acetate functional group ( synthetic name:

1E,3Z,4S,6E)-3-(Acetoxymethylene)-7,11-dimethyl-1,6,10-dodecatrien-8-yne-1,4-diyl diacetate ;

chemical formula: C₂₁H₂₆O₆) isolated from Caulerpa taxifolia is a toxic compound induces cell

death by interfering tubulin polymerization. X ray diffraction study shown that it induces

aggregation of tubulin units on cell periphery and disables microtubule network forming. It was

tested positive against neuroblastoma SK-N-SH cell lines [30]. Caulerpenyne, was also found to

be antiproliferative against KB cells and colorectal cancer cells in µM ranges [31]. Aqueous

extracts of Chlorella increased cell death in DMBA induced breast cancer in rats inducing pro-




apoptotic pathway[32]. .Green algae Cladophoropsis vaucheriaeformis also have effective anti

tumorogenic properties against murine lymphoid leukemia L1210 cells and for low cytotoxic

activity against NIH-3T3 normal cells [33].

Red algae (Rhodophyceae):

Dichloromethane: methanol fraction from rhodophycean species Bryothamnion triquetrum with

active concentration of 8.2 ± 1.3 µg/ml was evaluated against HEp-2 human cancer cell line[27].

Red algae Porphyra yezonensis and Eucheuma gelatinae showed significant inhibition to cancer

cells. Rhodophycean genera Amphiroa zonata contains palmetic acid, which target tumor cell’s

DNA topoisomerase I; shows in vivo antitumor activity in mice which also induces apoptosis in

MOLT4(acute lymphoblastic leukemia) cancer cell line with an IC₅₀ dose of 50μg/ml [34].

cold water sea weed Porphyra sp. a Rhodophycean algae was effectively shown to control

proliferation of Breast cancer cells. Various sterols like, campesterol, cholesterol, 22-

dehydrocholesterol, desmosterol, fucosterol, ß sitosterol and stigmasterol are found in this algae

[35]. Methanolic extract of red algae Gracilaria tenuistipitata was found to induce sub G1

accumulation in Ca9-12 (Oral cancer cell line) and it shown increased ROS generation, GSH

depletion, caspase activation and subsequent cell death .In the treated cells Annexin positive and

γ H2AX positive cells increased significantly indicating induction of cell death due to DNA

damage .MTS based cell viability assay was found to be effective with an IC₅₀ dose of 326μg/ml.

[36]. Another red algae Lithothamnion calcarium’s extract was found to be effective against

colon cancer [37]. MTT assay showed that best cytotoxic effect obtained from dichloromethane

extract and chloroform fraction of Hypnea musciformis on K562 (chronic myelolytic leukemia)

cell line with an effective concentration of 3.8 ± 0.2 µg/ml and 6.4 ± 0.4 µg/ml [38]. Chloroform

fraction of Hypnea musciformis showed anti cancerous activity on HEp-2 (laryngeal epidermal

carcinoma) cell line and the effective concentration was 6.0 ± 0.03 µg/ml [38]. Chloroform

fraction of H. musciformis showed cytotoxic properties against NCI- H292 cell line (human lung

mucoepidermal carcinoma),with an effective dose of 15.0 ± 1.3 µg/ml [38]. Methanolic

extraction of Plocamium telfairiae was reported to induce caspase independent cell death in HT-

29 human colon carcinoma cells. [39]. Plocamium corallorhiza and Plocamium cornutum contain

polyhalogenated monoterpene compound sargaquinoic acid (SQA) and (RU015); SQA was able




to induce apoptosis in breast cancer cell line MDA-MB-231, with 50% inhibition occurred at 6

μM range. RU015, induces necrosis [40]

Anti-cancerous and anti tumorous efficiencies of edible marine seaweed Palmaria palmate were

reported [41].

Condriamide-A isolated from Chondria sp shown to be active against human KB and colorectal

cancer cell lines LOVO; with an active concentrations of 0.5 μg/ml and 5μg/ml respectively [42].

Alcoholic extracts of some marine sea-weed Acanthaphora spicifera exhibited high cytotoxicity

in Ehrilch’s ascites carcinoma cells [43]. Halomon isolated from red algae Portieria hornemannii

is a polyhalogeneted monoterpene ((3S,6R)-6-Bromo-3-(bromomethyl)- 2,3,7-trichloro-7-methyl-

1-octene) C₁₀H₁₅Br₂Cl₃ is found to be toxic against many marine fauna but its active anti

cancerous properties was approved by NCI against brain, colon and renal cancer cell lines (Hl

60TB, MOLT-4, K562, HCT 116, Ht 29, OVCAR, A498 etc.) but showed selectively lesser

cytotoxicity against melanoma and leukemia cell lines[44]. Laurenmarianol and (21A) 21 –

hydroxythyrsiferol were isolated and identified from Laurencia mariannensis showed cytotoxicity

against p388 tumor cell with an IC 50 doses of 0.6 and 6.6 mg/ml respectively. 16-hydroxy

dehydrothyrsiferol, thyresenol A and thyresenol B isolated from Laurencia viridis also showed

cytotoxicity in p388 cells. From another species of Laurencia, (L. obtuse ) five more cytotoxic

triterpenoids were also isolated. Four bromophenols isolated from Rhodomela confervoides

showed antitumor activities against human epithelial tumor cell (KB), human hepatocellular

carcinoma (Bel 7402) and lung cancer cell (A549) .Among these compounds, compound 1(

3bromo-4, 5dihydroxy benzoic acid methyl ester) showed most efficacy against all the three

tumor cells with an IC50 dose of 3.09 μg/ml.[45]. Champia feldmannii contain novel sulfeted

polysaccarides showed anti-tumor activity against sarcoma 180 tumor cells [46].

Brown Algae:

Brown algae Himantothallus grandifolius ethanolic extract was reported to have suppressed cell

proliferation and promote apoptosis-mediated cell death with induction of initial stages of

apoptosis in different epithelial tumour cell lines (A375, A549, Hep-2,HeLa) compared to non-

malignant cell line (Hek-293) [47]. Dichloromethane: methanol fraction from Pheophycean

genera Lobophora vairegata and Dictyota caribaea, with an effective concentrations of 26.2 ±

1.3 µg/ml and 27.9 µg/ml were evaluated and result showed positive anti cancerous activity on

human cancer cell line KB [27]. Edible sea weed Undaria pinnatifida extracts was effectively

shown to control proliferation of breast cancer cells[48]. Methanolic extract of Padina pavonia




showed cytotoxic activity with an IC50 values of 86.45 μg/ml and 74.59 μg/ml in HeLa (

cervical cancer cell line), and MDA-MB-453 (breast cancer cell line) respectively [49].

Dichloromethane extract of Dictyota dichotoma and Padina gymnospora showed anti cancerous

activity on HEp-2 (laryngeal epidermal carcinoma) cell line and the effective concentrations were

16.3 ± 0.3 µg/ml and 8.2 ± 0.4 µg/ml respectively [38]. Whereas ethanolic extraction of Padina

gymnospora at an effective dose of 15.0 ± 2.8 µg/ml , showed cytotoxicity against NCI- H292

(human lung mucoepidermal carcinoma)cell line [38]. Brown algae Stypodium sp., has active

compound Stylopoldione that interferes with spindle formation and can be used in alternative

therapeutics [50]. Crude extracts of Scytosiphon lomentaria, Cystoseira mediterranea, Padina

pavonica, Hypnea musciformis, Spyridia filamentosa showed potent cytotoxicity in the

concentration range of 100-200 µg ml-1

with 24 hours incubation time tested on three cell lines

MCF-7,DU145, LNCaP, PC3 [51].

Heterofucan SF-1.5V is a form of sulphated L-fucose isolated from Sargassum filipendula

characterized as a very useful anti carcinoganic drug examined on cervical cancer cell line HeLa.

It was found to be very effective inducing cell death as this drug releases mitochondrial Apoptosis

inducing factor (Apaf) into cytosol and at the same time decreases anti apoptotic factor Bcl-2 and

increases the level of apoptosis inducing factor Bax [52]. Due to presence of sulfated

polysaccharide fucoidan, extract of Sargassum mcclurei showed anti cancerous activity against

DLD-1 colon cancer cell line with the concentrations ranging from 1 to 200 µg/ml [53]. Ethanolic

extract of Sargassum wightii containing novel polysaccharide exibited anti proliferative

properties against AGS, HeLa, MCF-7, PC12 cell lines by inducing apoptotic cascade with an

IC₅₀ doses of 43.61 ± 4.1, 46.92 ± 3.6, 99.38 ± 2.9, 158.8 ± 5 lg/mL for each cell lines

respectively [54]. Polysaccharide extracted from the brown alga, Sargassum latifolium (ethanolic

extract derivative) have been proved to have antiproliferative potential against human

lymphoblastic leukemia and the IC₅₀dose was found to be significantly lower(17.18 μg/ml), the

extract not only induced apoptosis but also able to induce the carcinogen detoxification enzyme

glutathione-S-transferases [55]. Sargassum heterophyllum contain novel compound sargaquinoic

acid, that induced apoptotic pathway by activating caspase -3, -6, -8, -9 -13 and down regulating

Bcl-2 protin level in metastatic MDA-MB-231 breast cancer cells with an IC50 dose of

67μM.[40]. Anti-cancer activity of aqueous extract of brown algae Sargassum oligocystum

proved its effectiveness for treating cancer cell lines Daudi and K562 with an effective IC50

doses of 500µg/ml and 400µg/ml [56]. Leathesia nana extract, rich in BromoPhenol, containing




one or several benzene rings, a varying degree of bromine and hydroxyl-substituents, could

inhibit the growth of Sarcoma 180 tumors in vivo and improve the immune system remarkably

[57].

Brown algae Stypopodium flabelliforme contain a novel stypodiol compound 14-keto-stypodiol

diacetate (SDA) which was tested aginst human prostate cancer cell line (DU-145), found to be an

effective anti-microtubule polymerization compound by inhibiting cell growth at about 61% with

purified SDA at 45μM concentration. [58].

Epitaondiol and stypotriol two meroditrpenoid extracted from Stypopodium flabelliforme exibit

50% inhibition in human neuroblastoma (SH-SY5Y) cell line at the concentration of 12.2 μM

and 14 μM respectively. Varying concentrations of three compounds stypotriol triacetate,

epitaondiol monoacetate and epitaondiol also inhibit adenocarcinoma (Caco-2) and rat basophilic

leukemia (RBL-2H3) cell lines [59].

Fucoxanthin extracted from various brown algae such as hijikin (Sargassum fusiforme), kombu

(Laminaria japonica), and wakame(Undaria pinnatifida); found to be an effective apoptosis

inducing compound tested against prostate cancer cell line PC-3, DU 145 and LNCaP; with a

concentration of 20 μmol/L which exibited significant inhibition of cell proliferation of about

86%, 95% and 90% in these three cell lines respectively [60]. Undaria pinnatifida contains

fucoidan , which were screened for antitumor activity and appreciable inhibition of Ehrlich

carcinoma tumor cells was found [61]. Fucoxanthinol now been established as a potent anti

carcinogenic compound and a study was done to evaluate the efiicacy of the pure fractioned

fucoxanthin and its metabolites produced into the gastrointestinal tract against human prostate

cancer cells(PC-3). Fucoxanthin metabolized into fucoxanthinol and finally amarouciaxanthin A

.Fucoxanthin, fucoxanthinol, and amarouciaxanthin A, exibited 50% cell growth inhibition of

PC-3 cells at 3.0, 2.0, and 4.6 μM concentrations respectively [62]. In vivo studies with seaweed

Acanthaphora spicifera extract was found to be more effective to treat Ehrlich’s ascites

carcinoma cells than conventional chemotherapeutic drug 5-flurouracil and showed better

tumoricidal capability in mice model by decreasing tumor size and increasing viable cell count

[63]. Brown algae Ascophyllum nodosum has anti-tumor activity tested against sigmoid colon

adenocarcinoma cells and its isolated fucoidin proved to be a potent anti-cancerous and anti-

tumorous agent [64]. Phaeophycean algae Sargassum thunbergii contains novel fucoidin, GIV-A,

a L-fucan sulfate; in vivo studies in mice also suggest its effectiveness as well, it showed

enhancement of phagocytic macrophages, resulting enhancemanet of immune response [65].




Meroterpenes, usneoidone E and usneoidone Z , isolated from the chloroform extract of

Cystoseira usneoides showed antitumor properties against L-1210 cell line(lymphocytic leukemia

[66]. Brown algae Fucus evanescens contains sulfated polysaccharides which showed anti-tumor

activity in mice, transplanted with Lewis lung adenocarcinoma [67]. Evidence of anti cancerous

activities of brown alga like Scytosiphon lomentaria, Lamineria japonica, Sargassum

ringgoldianum, Lessonia nigrescens against Ehrlich carcinoma [29] has also been found. The

percentage of inhibition was 69.8% for Scytosiphon lomentaria extract, 60% for Lessonia

nigrescensextract, 57.6% inhibition for Lamineria japonica, 45.6% inhibition for Sargassum

ringgoldianum extract .

CONCLUSION

Diverse types of chemicals isolated and chraterized from algal origin( from unicellular

cyanophyceae to green, brown and red algae) have been proved to be efficient as anti

proliferative and anti tumorogenic compound. Many of these chemicals obtained from algal

extract contain active compounds,such as, diverse types of water soluble or alcohol soluble

polysaccharides or fucoidan or sulfated polysaccharide, metal containing polyketides,varous types

of alkaliods, sterol, depsipeptides, halogenated or sesquiterpenes, phenol derivatives, carotenoids,

diverse forms of stypodiols etc. Most of them induce cell death either by inducing apoptotic

pathway by activating caspases; or by interfering with cellular microtubule nucleation or by

forming inter cellular caspase independent auto-phagosome. Anti cancerous and anti tumorogenic

compounds derived from algal origin needs clinical trials and advance molecular characteriziton

to support the effecacy of these compounds. Future biological research along with detailed

chemical characterization are needed to establish alga derived anti cancerous activity more

firmly.

ACKNOWLEDGEMENT

The authors wish to thank WB-DST (Sanc. No- 778/(sanc.)/ ST/P/S&T/9G-14/2012) for the

financial assistance. We also thank Department Of Botany, Centre Of Advanced Study,

University Of Calcutta; Kolkata-700019.

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