期刊
BIOLOGICAL & PHARMACEUTICAL BULLETIN
卷 34, 期 10, 页码 1553-1558出版社
PHARMACEUTICAL SOC JAPAN
DOI: 10.1248/bpb.34.1553
关键词
rhizochalin; AMP-activated protein kinase; c-Fos; c-Jun; cell transformation
资金
- Chosun University
Rhizochalin is a two-headed sphingolipid-like compound isolated from the sponge Rhizochalina incrustata. It has been reported that rhizocalin and its derivates have a chemopreventive and chemotherapeutic effect. However, the molecular mechanism of these effects is not understood. Here, we demonstrate that aglycon of rhizochalin (AglRhz) from the Rhizochalina incrustata induces AMP-activated protein kinase (AMPK) phosphorylation, and thereby inhibits mammalian target of rapamycin (mTOR)-p70S6 kinase-extracellular signal-regulated kinase (ERK) signaling and activator protein 1 (AP-1) activity via phosphorylation of Raptor in HT-29 cells. In addition, AglRhz induced activation of caspase-3 and poly(ADP-ribose) polymerase (PARP), and DNA fragmentation in HT-29 cells, leads to induction of apoptosis as well as suppression of tumorigenicity of HT-29 cells. Notably, AglRhz inhibits insulin-like growth factor (IGF)-1-induced AP-1 activity and cell transformation in JB6 CI41 cells. Overall, our findings identify AMPK as an important target protein for mediating the antitumor properties of AglRhz in HT-29 colon cancer cells and have important implication for sponges, the most important marine source, in colon cancer.
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