Overaccumulation of p53-mediated autophagy protects against betulinic acid-induced apoptotic cell death in colorectal cancer cells.

ABSTRACT: Betulinic acid (BA) exhibits cytotoxic activity against some cancer cells. However, the molecular mechanism of BA against CRC cells was little reported. Here, we proved that BA elicited CRC cells' growth inhibition and apoptosis in a dose-dependent manner. In addition, BA treatment induced autophagy via inhibiting the AKT-MTOR signaling pathway. Inhibition of autophagy by either administration of autophagic inhibitor chloroquine or siRNA-mediated knockdown of ATG5 could augment BA-induced apoptotic cell death as well as inhibition of cell proliferation. Moreover, we found that p53 was firstly activated by short exposure to BA and then was rapidly degraded via the ubiquitin-mediated degradation pathway in both wtp53 and mutp53 CRC cells. Notably, more preferential cytotoxicity of BA was obt

SUBMITTER: Wang S 

PROVIDER: S-EPMC5682653 | biostudies-literature | 2017 Oct

REPOSITORIES: biostudies-literature