Hirsutanol A induces apoptosis and autophagy via reactive oxygen species accumulation in breast cancer MCF-7 cells

Hirsutanol a is a novel sesquiterpene compound purified from the marine fungus chondrostereum sp in the coral sarcophyton tortuosum. our previous studies had demonstrated that hirsutanol a exerted potent cytotoxic effect in many kinds of cancer cell lines. here,the anticancer molecular mechanisms of hirsutanol a were investigated in breast cancer mcf-7 cells. the results showed that hirsutanol a could inhibit cell proliferation,elevate reactive oxygen species (ros) level,and induce apoptosis and autophagy. co-treatment with the potent antioxidant agent n-acetyl-l-cysteine could effectively reverse the effect of enhanced ros production,which in turn,reduces growth inhibition,apoptosis,and autophagy mediated by hirsutanol a. in addition,blocking autophagy by bafilomycin a1 or atg7-sirna could synergistically enhance the antiproliferative effect and apoptosis induced by hirsutanol a. these data suggested that hirsutanol a could induce apoptosis and autophagy via accumulation of ros and co-treatment with an autophagy inhibitor could sensitize mcf-7 cells to hirsutanol a. © the japanese pharmacological society.