RETRACTED: Apoptotic Effects of Rotundic Acid on Human Esophagus and Lung Cancer Cells

Abstract

Rotundic acid (RA) is a pentacyclic triterpenic acid. Apoptotic effects of RA at 4, 8, or 16 microM in OE33 and A549 cell lines, an esophageal squamous cancer cell line and a non-small-cell lung cancer cell line, were examined. RA at 4 to 16 microM inhibited the survival of both cell lines. RA at 8 and 16 microM decreased Bcl-2 expression and at 4 to 16 microM upregulated Bax and cleaved caspase-3 expression. RA treatments decreased the ratio of Bcl-2/Bax in those cells. RA at 4 to 16 microM lowered Na+-K+-ATPase activity and reduced mitochondrial membrane potential in OE33 and A549 cells. RA at 8 and 16 microM enhanced DNA fragmentation and caspase-3 and caspase-9 expression in OE33 cells. In A549 cells, RA increased caspase-3 expression in a concentration-dependent manner; but only at 8 and 16 microM, it upregulated caspase-9 expression. RA treatments at 4 to 16 microM decreased protein kinase c activity, suppressed the expression of cytochrome c and apoptosis-inducing factor, and lowered the production of reactive oxygen species, vascular endothelial growth factor, transforming growth factor-beta1, and tumor necrosis factor-alpha in both cell lines. RA at 8 and 16 microM downregulated hypoxia-inducible factor-1alpha expression. These findings suggest that RA could penetrate into OE33 and A549 cells and execute cytotoxic activities.