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Luteolin induces apoptotic cell death through AIF nuclear translocation mediated by activation of ERK and p38 in human breast cancer cell lines
Author(s) -
Kim Moon Jung,
Woo Jae Suk,
Kwon Chae Hwa,
Kim Jae Ho,
Kim Yong Keun,
Kim Ki Hyung
Publication year - 2012
Publication title -
cell biology international
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.932
H-Index - 77
eISSN - 1095-8355
pISSN - 1065-6995
DOI - 10.1042/cbi20110394
Subject(s) - apoptosis , mapk/erk pathway , p38 mitogen activated protein kinases , programmed cell death , chromosomal translocation , cancer research , microbiology and biotechnology , luteolin , human breast , chemistry , cell , cancer , cell culture , kinase , cancer cell , biology , biochemistry , genetics , antioxidant , gene , quercetin
The flavonoid, luteolin, has been shown to have anticancer activity in various cancer cells; however, the precise molecular mechanism of its action is not completely understood, and studies were conducted to find out how it induces apoptosis in breast cancer cells. Luteolin induced a reduction of viability in a dose‐ and time‐dependent manner. The pro‐apoptotic effect of luteolin was demonstrated by cell cycle measurement and Hoechst 3325 staining. Western blot analysis showed that luteolin activates ERK (extracellular‐signal‐regulated kinase) and p38. Pharmacological inhibition or knockdown of ERK and p38 protected against luteolin‐induced cell death; however, the caspase‐3‐specific inhibitor had no effect. Immunocytochemical examination indicated that luteolin induced nuclear translocation of AIF (apoptosis‐inducing factor), which was mediated by activation of ERK and p38. Transfection of a vector expressing the miRNA (microRNA) of AIF prevented luteolin‐induced apoptosis. The data suggest that luteolin induces a caspase‐dependent and ‐independent apoptosis involving AIF nuclear translocation mediated by activation of ERK and p38 in breast cancer cells.