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Kaempferol induces apoptosis through mitochondria‐mediated events: Mediation by the inactivation of Akt
Author(s) -
An Min Ji,
Cho Han Jin,
Park Jung HY
Publication year - 2007
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.21.5.a360-b
Subject(s) - kaempferol , apoptosis , protein kinase b , cytochrome c , chemistry , mitochondrion , microbiology and biotechnology , western blot , biology , biochemistry , quercetin , antioxidant , gene
A vast of naturally occurring substances have been shown to protect against experimental carcinogenesis and an increasing amount of evidence suggests that flavonoids may been have cancer chemopreventative properties. We previously observed that kaempferol, one of the flavonoids, inhibit cell proliferation by inducing cell cycle arrest and stimulating apoptosis in HT‐29 cells. To study the mechanisms by which kaempferol increases apoptosis, cells were treated with various concentrations (0, 20, 40, and 60 μmol/L) of kaempferol. Western blot analysis and in vitro kinase assay revealed that kaempferol decreased the phosphorylation of Akt levels and Akt kinase activity. Kaempferol did not alter bad protein levels but increased translocation of Bad to mitochondria. Also, kaempferol decreased Bcl‐xL and increased Bik protein levels. Kaempferol increased permeability of the mitochondrial membrane, and induced release of cytochrome c from mitochondria to cytoplasm. In addition, kaempferol increased levels of cleaved caspase‐9, ‐3, ‐7 and cleaved poly (ADP‐ribose) polymerase. These results indicate that kaempferol induces apoptosis through the event associated with mitochondria, which may be mediated it ability to inactivate Akt.