Betulinic acid inhibits the proliferation of human laryngeal carcinoma cells through reactive oxygen species-mediate mitochondrial apoptotic pathway

Abstract

Betulinic acid (BA), a natural pentacyclic triterpene, was extracted from the white birch tree, Triphyophyllum peltatum and the jujube tree. In a variety of human cancer cell lines, this substance displays anticancer properties. In this study, we examined how BA works to inhibit human laryngeal cancer growth. We discovered that BA minimally exhibited cytotoxicity in normal cells (human normal cell line GES-1), while remarkably inhibiting viability of AMC-HN-8, TU212, HEp-2 and M4e cells in a concentration-dependent manner. In AMC-HN-8 cancer cells, BA induced apoptosis, activated caspase-3/9/PARP, significantly reduced mitochondrial membrane potential (MMP), increased the expression of cytochrome C in the cytoplasm, transported Bax to the mitochondria, increased the production of reactive oxygen species (ROS), and the ROS scavenger N-acetylcysteine can reduce apoptosis. All data showed that BA triggered apoptosis via the mitochondrial pathway, in which ROS production was likely involved. The findings support the development of BA as a viable drug for the treatment of human laryngeal carcinoma.