Premium
Aciculatin, a C‐glycosidic flavonoid, induces p53‐dependent cell cycle arrest and apoptosis in HCT116 colorectal cancer cells
Author(s) -
Lai Chinyu,
Pan ShiowLin,
Chen ChienChih,
Teng CheMing
Publication year - 2011
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.25.1_supplement.621.7
Subject(s) - glycosidic bond , apoptosis , flavonoid , cell cycle checkpoint , colorectal cancer , chemistry , cancer research , cell cycle , cancer , biology , biochemistry , medicine , antioxidant , enzyme
Aciculatin, a flavonoid extracted from Elephantopus scaber L. , has an uncommon C‐glycoside structure and superior anti‐cancer activity. This study firstly demonstrates that aciculatin induces cells death in time‐ and dose‐dependent manners in HCT116. After 10 μM aciculatin treatment, cells arrest in G1 phase and undergo apoptosis subsequently. It is shown that tumor suppressor protein p53 accumulate in this pathway. We further compared WT and p53−/− HCT116 and found that p53−/− HCT116 is more resistant to aciculatin. The same results can be achieved by knockdown of p53 level in WT cells. These data suggest that p53 plays a crucial role in aciculatin‐induced apoptosis. Previous study has defined aciculatin a DNA‐binding agent in vitro . However, DNA damage signaling is not significant in this case, which implies there are some other events leading to p53 activation. Furthermore, aciculatin can down‐regulate MDM2, the negative regulator of p53, in early stage. This may contribute to p53 accumulation. Taken all together, these results indicate that aciculatin induces G1 arrest and apoptosis of HCT‐116 cells via p53 activation.