Pro-apoptotic effects of the novel tangeretin derivate 5-acetyl-6,7,8,4'-tetramethylnortangeretin on MCF-7 breast cancer cells.
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| Abstract |
Citrus polymethoxyflavone tangeretin (5,6,7,8,4'-pentamethoxyflavone, TAN) displays multiple biological activities, but previous reports showed that TAN failed to induce MCF-7 human breast cancer cells apoptosis. Herein, we prepared 5-acetyl-6,7,8,4'-tetramethylnortangeretin (5-ATAN), and evaluated its cytotoxicity on MCF-7 cells. 5-ATAN revealed stronger cytotoxicity than that of parent TAN in the growth inhibition of MCF-7 cells. 5-ATAN induced apoptosis via both caspase-independent and -dependent pathways, in which 5-ATAN induced the translocation of apoptosis inducing factor and phosphorylation of H2AX as well as poly (ADP-ribose) polymerase cleavage, caspase-3 activation. However, 5-ATAN did not affect extrinsic markers caspase-8, BID, and FADD. Further, 5-ATAN induced the loss of mitochondrial membrane potential (Δψm) by regulating the Bax/Bcl-2 ratio. Loss of Δψm led to the mitochondrial release of cytochrome c which triggered activation of caspase-9. In conclusion, these data indicate that 5-ATAN plays pro-apoptotic cytotoxic roles in MCF-7 cells through both caspase-dependent intrinsic apoptosis and caspase-independent apoptosis pathways.
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| Authors | Jinhan Wang, Yitao Duan, Dexian Zhi, Guangqiang Li, Liwen Wang, Hongmei Zhang, Lichao Gu, Haihua Ruan, Kunsheng Zhang, Qiang Liu, Shiming Li, Chi-Tang Ho, Hui Zhao |
| Journal | Cell biochemistry and biophysics (Cell Biochem Biophys) Vol. 70 Issue 2 Pg. 1255-63 (Nov 2014) ISSN: 1559-0283 [Electronic] United States |
| PMID | 24938898 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't) |
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