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.
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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