Pharmacological inhibition of protein kinase C activity could induce apoptosis in gastric cancer cells by differential regulation of apoptosis-related genes

The protein kinase C (PKC) signaling pathway plays a key role in tumor cell proliferation, differentiation, and apoptosis. Gastric cancer usually poss esses a higher level of PKC activity than normal tissue. We evaluated inhib ition of PKC activity in apoptosis induction of gastric cancer cells and th e expression profile of apoptosis related genes. Gastric cancer cells (AGS) were incubated with two highly specific PKC inhibitors (RO-31-8220 and che lerythrine). Cell viability and cell cycle were determined by methyl-tetraz olium (MTT) assay and flow cytometry, respectively. Apoptosis was character ized by acridine orange staining, DNA gel electrophoresis, and flow cytomet ry. The expression of p53, p21(waf/cip1), c-myc, bcl-2, and bar was determi ned by western blot. The results showed that both PKC inhibitors hindered c ell growth, arrested cells at G(0)/G(1) phase and induced apoptosis. The pr otein level of p53, p21(waf/cip1), c-myc, and bar was elevated while bcl-2 kept unchanged following drug exposure. In conclusion, PKC inhibitors suppr ess growth of gastric cancer cells through apoptosis induction and cell cyc le quiescence, which may be regulated by differential expression of apoptos is-related genes.