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Curcumin Induces both Apoptosis and Autophagy in Human Papillary Thyroid Carcinoma BCPAP Cells Zhang Li Jiangsu Institute of Nuclear Medicine Wuxi, Jiangsu, China Contact: [email protected] 10 th AOTA Congress BALI, INDONESIA, 2012

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Page 1: Curcumin Induces both Apoptosis and Autophagy in Human Papillary Thyroid Carcinoma BCPAP Cells Zhang Li Jiangsu Institute of Nuclear Medicine Wuxi, Jiangsu,

Curcumin Induces both Apoptosis and Autophagy in Human Papillary Thyroid Carcinoma BCPAP Cells

Zhang Li Jiangsu Institute of Nuclear Medicine

Wuxi, Jiangsu, China

Contact: [email protected]

10th AOTA CongressBALI, INDONESIA, 2012

Page 2: Curcumin Induces both Apoptosis and Autophagy in Human Papillary Thyroid Carcinoma BCPAP Cells Zhang Li Jiangsu Institute of Nuclear Medicine Wuxi, Jiangsu,

Curcumin

An acitve polyphenol derived from the plant turmeric

low toxicity

anti-inflammatoryantioxidantantiangiogenic antitumour

Chemical structure of curcumin

Curcumin Thyroid cancer ?

Page 3: Curcumin Induces both Apoptosis and Autophagy in Human Papillary Thyroid Carcinoma BCPAP Cells Zhang Li Jiangsu Institute of Nuclear Medicine Wuxi, Jiangsu,

Apoptosis and Autophagy

Apoptosis –type I programmed cell death

Autophagy- type II programmed cell death

- a self-degradative process

- cope with stresses

- required in apoptotic-deficient cells

Three types of autophgay:

- Microautophagy- Chaperone-mediated autophagy- Macroautopahgy

Page 4: Curcumin Induces both Apoptosis and Autophagy in Human Papillary Thyroid Carcinoma BCPAP Cells Zhang Li Jiangsu Institute of Nuclear Medicine Wuxi, Jiangsu,

Part I

Crucumin suppresses BCPAP cells growth

Page 5: Curcumin Induces both Apoptosis and Autophagy in Human Papillary Thyroid Carcinoma BCPAP Cells Zhang Li Jiangsu Institute of Nuclear Medicine Wuxi, Jiangsu,

A B

Effects of curcumin on cell viability

Page 6: Curcumin Induces both Apoptosis and Autophagy in Human Papillary Thyroid Carcinoma BCPAP Cells Zhang Li Jiangsu Institute of Nuclear Medicine Wuxi, Jiangsu,

Effects of curcumin on cell morphology

Page 7: Curcumin Induces both Apoptosis and Autophagy in Human Papillary Thyroid Carcinoma BCPAP Cells Zhang Li Jiangsu Institute of Nuclear Medicine Wuxi, Jiangsu,

PI/Hoechst 33342 staining

A B

Page 8: Curcumin Induces both Apoptosis and Autophagy in Human Papillary Thyroid Carcinoma BCPAP Cells Zhang Li Jiangsu Institute of Nuclear Medicine Wuxi, Jiangsu,

Part II

Curcumin induces apoptosis in BCPAP cells

Page 9: Curcumin Induces both Apoptosis and Autophagy in Human Papillary Thyroid Carcinoma BCPAP Cells Zhang Li Jiangsu Institute of Nuclear Medicine Wuxi, Jiangsu,

Effects of curcumin on pro-apoptotic and anti-apoptotic proteins

A

B

Page 10: Curcumin Induces both Apoptosis and Autophagy in Human Papillary Thyroid Carcinoma BCPAP Cells Zhang Li Jiangsu Institute of Nuclear Medicine Wuxi, Jiangsu,

Effects of curcumin on loss of mitochondrial membrane potential (MMP)

Page 11: Curcumin Induces both Apoptosis and Autophagy in Human Papillary Thyroid Carcinoma BCPAP Cells Zhang Li Jiangsu Institute of Nuclear Medicine Wuxi, Jiangsu,

Caspase-dependent apoptosis in

curcumin-treated cells

Page 12: Curcumin Induces both Apoptosis and Autophagy in Human Papillary Thyroid Carcinoma BCPAP Cells Zhang Li Jiangsu Institute of Nuclear Medicine Wuxi, Jiangsu,

Part III

Curcumin induces autophagy in BCPAP cells

Page 13: Curcumin Induces both Apoptosis and Autophagy in Human Papillary Thyroid Carcinoma BCPAP Cells Zhang Li Jiangsu Institute of Nuclear Medicine Wuxi, Jiangsu,

Induction of autophagy in curcumin-treated cells

A

B

The FASEB JournalJune 2003vol. 17 no. 9 1165-1167

Page 14: Curcumin Induces both Apoptosis and Autophagy in Human Papillary Thyroid Carcinoma BCPAP Cells Zhang Li Jiangsu Institute of Nuclear Medicine Wuxi, Jiangsu,

RF

P-L

C3

Curcumin (mM)

0 50

C

Induction of autophagy in curcumin-treated cells

Page 15: Curcumin Induces both Apoptosis and Autophagy in Human Papillary Thyroid Carcinoma BCPAP Cells Zhang Li Jiangsu Institute of Nuclear Medicine Wuxi, Jiangsu,

Effects of curcumin on the phosphorylation of AKT pathway

A

B

Page 16: Curcumin Induces both Apoptosis and Autophagy in Human Papillary Thyroid Carcinoma BCPAP Cells Zhang Li Jiangsu Institute of Nuclear Medicine Wuxi, Jiangsu,

Effects of curcumin on the phosphorylation of MAP kinases

Page 17: Curcumin Induces both Apoptosis and Autophagy in Human Papillary Thyroid Carcinoma BCPAP Cells Zhang Li Jiangsu Institute of Nuclear Medicine Wuxi, Jiangsu,

Curcumin selectively induces autopagy in tumor cells

A

B

Page 18: Curcumin Induces both Apoptosis and Autophagy in Human Papillary Thyroid Carcinoma BCPAP Cells Zhang Li Jiangsu Institute of Nuclear Medicine Wuxi, Jiangsu,

Curcumin seletively induces cancer cell death

A B

Page 19: Curcumin Induces both Apoptosis and Autophagy in Human Papillary Thyroid Carcinoma BCPAP Cells Zhang Li Jiangsu Institute of Nuclear Medicine Wuxi, Jiangsu,

Dynamic distribution of curcumin in BCPAP cells

Enlarged

6 h

12 h

24 h

Page 20: Curcumin Induces both Apoptosis and Autophagy in Human Papillary Thyroid Carcinoma BCPAP Cells Zhang Li Jiangsu Institute of Nuclear Medicine Wuxi, Jiangsu,

Effects of curcumin on DNA conformation

A

B

Page 21: Curcumin Induces both Apoptosis and Autophagy in Human Papillary Thyroid Carcinoma BCPAP Cells Zhang Li Jiangsu Institute of Nuclear Medicine Wuxi, Jiangsu,

Conclusions

Curcumin induces cytotoxicity of BCPAP cells.

Induction of  apoptosis  and autophagy as the likely underlying mechanism that is responsible for the cytotoxicity of curcumin .

Curcumin inhibited AKT pathway and activated mitogen-activated protein kinase (MAPK) signaling thereby inducing autophagy.

Page 22: Curcumin Induces both Apoptosis and Autophagy in Human Papillary Thyroid Carcinoma BCPAP Cells Zhang Li Jiangsu Institute of Nuclear Medicine Wuxi, Jiangsu,

Bao Jiandong Yu Huixin Zhang Chiyu Wu Jing Zheng Jie Sun Wei

China Medical University

Guan Haixia

Nangjing University Sun Yang

AcknowledgementsJiangsu Institute of Nuclear Medicine Grants

National Natural Science Foundation of China (No. 30870727)

Natural Science Foundation of Jiangsu Province (No. BK2010156)

Science and Research Foundation of Health Bureau of Jiangsu Province (No. H2008031)