Tropical Journal of Pharmaceutical Research

Original Research Article | OPEN ACCESS

Betulinic acid inhibits glioma cell viability by down-regulation of NF-κB and enhancement of apoptosis

Zhu Yaozu^1,2, Yang Liu^1,3, Huang Zhao⁴, Peng Peng⁴, Zhang Tingbao¹, Chen Jincao¹

¹Department of Neurosurgery, Zhongnan Hospital of Wuhan University, Wuhan 430071; ²Department of Neurosurgery, Xiangyang Central Hospital, Affiliated Hospital of Hubei University of Arts and Science, Wuhan 441021; ³Department of Neurosurgery, General Hospital of Central Theater of the PLA, Wuhan 430070; ⁴Department of Neurosurgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, Hubei Province, PR China.

For correspondence:- Chen Jincao Email: chenjincao34@yahoo.com Tel:+862767813105

Accepted: 11 November 2020 Published: 30 December 2020

Citation: Yaozu Z, Liu Y, Zhao H, Peng P, Tingbao Z, Jincao C. Betulinic acid inhibits glioma cell viability by down-regulation of NF-κB and enhancement of apoptosis. Trop J Pharm Res 2020; 19(12):2545-2551 doi: 10.4314/tjpr.v19i12.9

© 2020 The authors.
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Abstract

Purpose: To determine the inhibitory potential of betulinic acid on pro-survival signaling pathway in glioblastoma.

Methods: Changes in viabilities of glioma cells and primary astrocytes were measured using 3-(4, 5dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) assay. Apoptotic changes were analyzed using Hoechst 33342 staining and Annexin V-FITC/PI kits. Western blotting was used for assaying the protein expressions of various pro-apoptotic and anti-apoptotic factors.

Results: The proliferative potential of U87MG and A172 cells were significantly reduced on treatment with betulinic acid in a concentration- and time-dependent manner. Treatment with betulinic acid at a dose of 8.75 µg/mL increased apoptosis in U87MG and A172 cells to 41.8 ± 0.5 and 48.8 ± 0.5%, respectively (p < 0.05). Betulinic acid significantly decreased intracellular levels of NFκB p65 and suppressed levels of survivin, XIAP and Bcl-2 in U87MG and A172 cells (p < 0.05). However, betulinic acid significantly increased the levels of Bax and activated caspase-9 and caspase-3 in U87MG and A172 cells (p < 0.05).

Conclusion: Betulinic acid inhibited the proliferation of U87MG and A172 glioblastoma cells and mediated their apoptosis. There is need for in vivo studies for validation of the therapeutic potential of betulinic acid as an anti-glioblastoma drug.

Keywords: Glioblastoma, Betulinic acid, Proliferation, Apoptosis, Chemotherapy, Intracranial malignancy