2-Oxonanonoidal Antibiotic Actinolactomycin Inhibits Cancer Progression by Suppressing HIF-1?.

ABSTRACT: 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 (ActinoLactoMycin), a compound extracted from metabolites of Streptomyces flavoretus, exhibits inhibitory effect on HIF-1?. Mechanistically, we found that ALM inhibited the translation of HIF-1? 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-1? inhibitor from the metabolites of Streptomyces flavoretus, which shows promising anti-cancer potential.

SUBMITTER: Cheng J 

PROVIDER: S-EPMC6563139 | biostudies-literature | 2019 May

REPOSITORIES: biostudies-literature