Involvement of protein kinase C-δ activation in betulin-induced apoptosis of neuroblastoma

Purpose: To investigate the clinical benefits and underlying mechanisms of action of betulin in the treatment of cancer using a neuroblastoma (NB) cell model. Method: Cell viability assay (MTT assay) was applied to investigate the effects of betulin on proliferation and apoptosis of SK-N-SH cell. The expression or translocation of apoptosis-related biomarkers, which include protein kinase C (PKC) family members, were analyzed and quantified by Western blotting, caspase activity assay or enzyme-linked immunosorbent assay (ELISA). Results: Betulin treatment significantly inhibited the growth of SK-N-SH cells (p < 0.001), with halfmaximal inhibition concentration (IC50) of 8 mu mol/ mL. Furthermore, betulin treatment increased the activity of PKC-d, which subsequently activated caspases 3, 8 and 9, thus initiating mitochondria-mediated endogenous apoptotic pathways in SK-N-SH cells Conclusion: Data generated in this study suggest that betulin inhibits cell proliferation and promotes apoptosis via PKC-d activation, which may provide new insights into NB treatment from the perspective of adjuvant chemotherapy and prevention of tumor recurrence.