Tropical Journal of Pharmaceutical Research

Original Research Article | OPEN ACCESS

Involvement of protein kinase C-^8; activation in betulin-induced apoptosis of neuroblastoma

Jin-hua Feng¹, Xiao-zheng Duan¹ , Jian-yu Pan², Wei-min Li³, Xu-dong Zhang², Yong-sheng Zhang⁴

¹Department of Pediatrics; ²Cardial Surgery Team of Encephalopathy Center; ³Neurosurgery Team of Encephalopathy Center, Affiliated Hospital to Changchun Traditional Chinese Medicine University; ⁴Department of Pediatrics, The First Hospital of Jilin University, Changchun, Jilin, 130000 China.

For correspondence:- Xiao-zheng Duan Email: XiaoZhengDuan@yeah.net

Accepted: 22 August 2017 Published: 30 September 2017

Citation: Feng J, Duan X, Pan J, Li W, Zhang X, Zhang Y. Involvement of protein kinase C-^8; activation in betulin-induced apoptosis of neuroblastoma. Trop J Pharm Res 2017; 16(9):2097-2105 doi: 10.4314/tjpr.v16i9.8

© 2017 The authors.
This is an Open Access article that uses a funding model which does not charge readers or their institutions for access and distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0) and the Budapest Open Access Initiative (http://www.budapestopenaccessinitiative.org/read), which permit unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited..

Abstract

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 half-maximal 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 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-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-^8;, Adjuvant chemotherapy, Tumor recurrence, Caspase