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Cheng, Jiadong; Hu, Lan; Yang, Zheng; Suo, Caixia; Wang, Yueyang Jack; Gao, Ping; Cui, Chengbin; Sun, Linchong
Cells, 05/2019, Volume: 8, Issue: 5Journal Article
HIF-1 serves as an important regulator in cell response to hypoxia. Due to its key role in promoting tumor survival and progression under hypoxia, HIF-1 has become a promising target of cancer therapy. Thus far, several HIF-1 inhibitors have been identified, most of which are from synthesized chemical compounds. Here, we report that ALM (Actino actoMycin , a compound extracted from metabolites of , exhibits inhibitory effect on HIF-1α. Mechanistically, we found that ALM inhibited the translation of HIF-1α protein by suppressing mTOR signaling activity. Treatment with ALM induced cell apoptosis and growth inhibition of cancer cells both in vitro and in vivo in a HIF-1 dependent manner. More interestingly, low dose of ALM treatment enhanced the anti-tumor effect of Everolimus, an inhibitor of mTOR, suggesting its potential use in combination therapy of tumors, especially solid tumor patients. Thus, we identified a novel HIF-1α inhibitor from the metabolites of which shows promising anti-cancer potential.
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