The Molecular Mechanisms Of Two Natural Anti-tumor Compounds

In this study, we studied the antitumor activity of two natural compounds.Oleanolic acid possesses a wide range of bioactivities. Our previous studies showedthat oleanolic acid induces apoptosis in tumor cells, but the mechanisms are stillunknown. Recently, it is well recognized that aerobic glycolysis (warburg effect) isone of the hallmarks of cancer biology and plays a critical role on the progression ofcancer. Pyruvate kinase M2(PKM2) is the key enzyme for enhanced aerobicglycolysis. More and more evidence showed that PKM2is a promising therapeutictarget for cancer. However, there are still no studies reporting that oleanolic acid canaffect aerobic effect. In this study, we employed several cancer cell lines to addressthis issue. The results revealed that oleanolic acid greatly suppressed the aerobicglycolysis (such as decreasing glucose uptakes by29.1%-30%, decreasing lactateproduction by16.2%-28.3%, increasing oxygen consumption by17.8%-54.5%).PKM2was found to switch to PKM1under the treatment of oleanolic acid.mTOR/c-Myc/hnRNPA1-hnPNPA2/PKM pathway was proved to be associated withthe effect of oleanolic acid.In this study, we also explored the synergistic effect of aplysin and TRAIL ontumor cells and the involved mechanisms. The data demonstrated that aplysinenhances the cytotoxicity of TRAIL by2.58-6.15folds through p38MAPK/survivinpathway.Collectively, our data confirmed that oleanolic acid suppresses aerobic glycolysisby decreasing PKM2abundance and aplysin enhances the sensitivity of cancer cells toTRAIL.