Critical Role of AMPK/Fox03A Axis in Globular Adiponectin-induced Cell Cycle Arrest and Apoptosis in Cancer Cells = Critical Role of AMPK/Fox03A Axis in Globular Adiponectin-induced Cell Cycle Arrest and Apoptosis in Cancer Cells

다국어 초록 (Multilingual Abstract)

Adiponeectin predominantly secreted from adipose tissue has exhibited potent anti- proliferative properties in cancer cells via modulating cell cycle and apoptosis, FoxO3A. a Forkhead box 0 member of the transcription factor. plays a critical role in modulating expression of genes involved In cell de:uh andlor SUrviV31. In this study. we investigated the role of FoxO3A signaling in and-cancer activities of adiponectin. Herein. we have shown that treaunent with globular adlponectln (gAcrp) Increases p27 but decreases cyclinD I expression In human hepatoma (HepG2) and breasr (MCF-7) cancer cells. Gene ablation of Fox03A prevented gAcrp-induced increase In p27 and decreased in cyelin 0 I expression. and further ameliorated cell cycle arrest by gAcrp.lndicating 3 critical role of FoxO3A in gAcrp-induced cell cycle arrest of cancer cells. Moreover, treatment with gAcrp also induced caspase-Jf7 activation and increased Fas ligand (Fasl) expression ln both HepG2 and MCF-7 cells. Transfecucn with FoxO3A siRNA inhibited gAcrp-induced caspase-3/7 activadon and Fasl expression. suggening that FoxO3A sigltaling also plays an lmportant role In gAcrp.induced apcptosis of cancer cells, We also found that gene silencing of AMPK prevented gAcrp-induced nuclear translocation of Fox03A in HepG2 and MCF-7 cells. In addition. suppression of AMPK also blocked gAcrp-lnduced cell cyele arrest and further attenuated gAcrp-induced caspase-3/7 activation, indICating that AMPK signaling plays a pivotal role in both gAcrp-lnduced cell cycle arrest and apoprosis via acting as an upstream S1gnalirlg of Fox03A Taken together. our firldings demonstrated that AMPK/Fox03A axis plays a cardinal role in anu-protlferanve effect of adiponecun in cancer cells.