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Jiangsu Institute of Nuclear Medicine Contact: zhangli@jsinm.org 10th AOTA Congress BALI, INDONESIA, 2012 Curcumin Induces both Apoptosis and Autophagy in Human Papillary Thyroid Carcinoma BCPAP Cells Zhang Li Jiangsu Institute of Nuclear Medicine Wuxi, Jiangsu, China Contact: zhangli@jsinm.org

Curcumin ? An acitve polyphenol derived from the plant turmeric low toxicity anti-inflammatory antioxidant antiangiogenic antitumour Curcumin Thyroid cancer ? Chemical structure of curcumin

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

Part I Crucumin suppresses BCPAP cells growth

Effects of curcumin on cell viability

Effects of curcumin on cell morphology

PI/Hoechst 33342 staining A B

Part II Curcumin induces apoptosis in BCPAP cells

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

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

Caspase-dependent apoptosis in curcumin-treated cells

Part III Curcumin induces autophagy in BCPAP cells

Induction of autophagy in curcumin-treated cells B The FASEB JournalJune 2003vol. 17 no. 9 1165-1167

Induction of autophagy in curcumin-treated cells RFP-LC3 Curcumin (mM) 50 C

Effects of curcumin on the phosphorylation of AKT pathway B

Effects of curcumin on the phosphorylation of MAP kinases

Curcumin selectively induces autopagy in tumor cells B

Curcumin seletively induces cancer cell death B

Dynamic distribution of curcumin in BCPAP cells Enlarged 6 h 12 h 24 h

Effects of curcumin on DNA conformation B

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.

Thank you for your attention! Acknowledgements Jiangsu Institute of Nuclear Medicine Grants Bao Jiandong Yu Huixin Zhang Chiyu Wu Jing Zheng Jie Sun Wei China Medical University Guan Haixia Nangjing University Sun Yang 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) Thank you for your attention!