Tropical Journal of Pharmaceutical Research

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Involvement of protein kinase C-δ activation in betulininduced apoptosis of neuroblastoma

Jin-hua Feng, Xiao-zheng Duan, Jian-yu Pan, Wei-min Li, Xu-dong Zhang, Yong-sheng Zhang


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 μmol/mL. Furthermore, betulin treatment increased the activity of PKC-δ, which subsequently activated caspases 3, 8 and 9, thus initiating mitochondriamediated 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-δ activation, which may provide new insights into NB treatment from the perspective of adjuvant chemotherapy and prevention of tumor recurrence.

Keywords: Betulin, Neuroblastoma, Apoptosis, protein kinase C-δ, Adjuvant chemotherapy, Tumor recurrence, Caspase
AJOL African Journals Online