title: Pro-apoptotic effects of the novel tangeretin derivate 5-acetyl-6,7,8,4'-tetramethylnortangeretin on MCF-7 breast cancer cells.
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.
authors.affiliation: Tianjin Key Laboratory of Food and Biotechnology, School of Biotechnology and Food Science, Tianjin University of Commerce, Tianjin, China.
authors.forename: Jinhan
authors.initials: J
authors.lastname: Wang
authors.forename: Yitao
authors.initials: Y
authors.lastname: Duan
authors.forename: Dexian
authors.initials: D
authors.lastname: Zhi
authors.forename: Guangqiang
authors.initials: G
authors.lastname: Li
authors.forename: Liwen
authors.initials: L
authors.lastname: Wang
authors.forename: Hongmei
authors.initials: H
authors.lastname: Zhang
authors.forename: Lichao
authors.initials: L
authors.lastname: Gu
authors.forename: Haihua
authors.initials: H
authors.lastname: Ruan
authors.forename: Kunsheng
authors.initials: K
authors.lastname: Zhang
authors.forename: Qiang
authors.initials: Q
authors.lastname: Liu
authors.forename: Shiming
authors.initials: S
authors.lastname: Li
authors.forename: Chi-Tang
authors.initials: CT
authors.lastname: Ho
authors.forename: Hui
authors.initials: H
authors.lastname: Zhao
mesh_terms: D000970:Antineoplastic Agents / Q000737:chemistry* / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D020169:Caspases / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D047309:Flavones / Q000737:chemistry* / Q000494:pharmacology*; D006801:Humans; D061986:MCF-7 Cells; D015398:Signal Transduction / Q000187:drug effects
chemical_list: C000598608:5-acetyl-6,7,8,4'-tetramethylnortangeretin; D000970:Antineoplastic Agents; D047309:Flavones; D020169:Caspases; C059006:tangeretin