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Activation of caspase‐8 contributes induction of apoptosis in HCT‐116 human colon cancer cells by the dietary compound fisetin
Author(s) -
Lim Doyoung,
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.a159-a
Subject(s) - fisetin , apoptosis , poly adp ribose polymerase , chemistry , cytochrome c , caspase , cancer cell , programmed cell death , microbiology and biotechnology , cancer research , biology , biochemistry , cancer , polymerase , enzyme , antioxidant , flavonoid , genetics
Fisetin, 3,3′,4′,7‐tetrahydroxyflavone, has been reported to inhibit proliferation of various cancer cells. It is present in fruits and vegetables, such as strawberry, apple, persimmon, and kiwi fruit. We have previously shown that fisetin inhibits cyclin dependent kinase activities leading to G1 and G2/M phase arrest in colon cancer cells. The present study examined whether fisetin induces apoptosis in HCT‐116 cells. DNA condensations and apoptotic cell numbers were increased in HCT‐116 cells treated with fisetin. Western blot analysis of total cell lysates revealed that fisetin increased the levels of cleaved caspsase‐9, ‐7 and ‐3, and cleaved poly (ADP‐ribose) polymerase. In addition, fisetin decreased anti‐apoptotic bcl‐xL and bcl‐2 levels and increased pro‐apoptotic bok, bak and bim protein levels. Fisetin also increased p53 protein levels but did not alter p53 mRNA levels. In addition, fisetin increased permeability of the mitochondrial membrane and induced cytochrome c and Smac/Diablo release. Furthermore, fisetin increased cleaved caspase‐8 and Fas‐ligand protein levels. Fisetin‐induced apoptosis and caspase 3 activation were suppressed by a caspase‐8 inhibitor. The present results indicate that fisetin induces apoptosis of HCT‐116 cells through activation of death receptor‐ and mitochondrial‐dependent pathway and subsequent activation of the caspase‐9/caspase‐3 cascade.