Tropical Journal of Pharmaceutical Research

Original Research Article | OPEN ACCESS

Effect of α-momordicine on proliferation and apoptosis of liver cancer, and its associated mechanisms of action

Mei Yang¹, Wen Jin¹, Wei Shi¹, Bo Wang¹, Qing Li²⁵, Chunfeng Guan²

¹Department of Medicine, Tongling Vocational and Technical College, 678 Furong Road, Hefei Economic Development Zone, Anhui Province; ²Department of Obstetrics and Gynecology, Second Affiliated Hospital of Anhui Medical University, Hefei, Anhui Province, China.

For correspondence:- Chunfeng Guan Email: xvk88f@163.com

Accepted: 29 August 2019 Published: 30 September 2019

Citation: Yang M, Jin W, Shi W, Wang B, Li Q, Guan C. Effect of α-momordicine on proliferation and apoptosis of liver cancer, and its associated mechanisms of action. Trop J Pharm Res 2019; 18(9):1935-1941 doi: 10.4314/tjpr.v18i9.22

© 2019 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 effect of α-momordicine (α-MMC) on liver cancer cell proliferation and apoptosis, and to elucidate the mechanisms of action involved.

Methods: In in vitro experiments, hepatoma cell lines were used, while nude mice with hepatocellular carcinoma were used for in vivo studies. Cancer cell proliferation was determined using MTT assay while apoptosis was assayed by flow cytometry and TUNNEL staining. Gene expression was determined with real-time polymerase chain reaction (RT-PCR), while protein expression levels were assayed by Western blot, immunohistochemistry and immunofluorescence.

Results: Alpha-MMC decreased HCC cell viability dose-dependently (p < 0.05). In HepG2 cells, G2/M cell cycle was halted after 48 h intervention with 1.24 mg/mL α-MMC. However, at G0/G1 phase, α-MMC at doses of 1.06 and 0.92 mg/mL caused cell cycle arrest of HCC-LM3 and SMMC-7721 cells. In vivo studies showed that after establishment of the nude mice liver cancer model, exposure to α-MMC at a dose of 0.70 mg/kg or 2.08mg/kg for 4 weeks reduced the size of liver cancer in the treatment group, relative to control group; mean diameter of liver cancer decreased from 2.16 to 0.51 cm, while mean volume decreased from 1.185 to 0.085 cm³. Moreover, α-MMC increased apoptosis level in liver cancer tissues in nude mice, and down-regulated the expressions of P-AKT, RAGE, MMP-9 and HMGB1, but upregulated Bax/Bcl2 ratio (p < 0.05).

Conclusion: α-MMC inhibits cancer cell growth and proliferation, and facilitates their apoptosis by positively regulating the ratio of Bax/Bcl2. The anti-liver cancer effect of α-MMC is mediated via HMGB1-RAGE and AKT signaling pathways.

Keywords: α-Momordicine, Liver cancer, Proliferation, Apoptosis