Tropical Journal of Pharmaceutical Research

Original Research Article | OPEN ACCESS

Excisanin A suppresses proliferation by inhibiting hypoxia-inducible factor-1? expression in human hepatocellular carcinoma cells

Li Zhuo Han¹, Changgao Jiang² , Chunliu Mi³, Ke Si Wang⁴, Hong Xiang Zuo¹, Zhe Wang¹, Ming Yue Li¹, Zhi Hong Zhang¹, Xuejun Jin¹

¹Key Laboratory of Natural Resources of Changbai Mountain & Functional Molecules, Ministry of Education, Molecular Medicine Research Center, College of Pharmacy, Yanbian University, Yanji 133002; ²Department of Gastroenterology, Affiliated Hospital of Yanbian University, Yanji 133000, Jilin Province; ³International Joint Research Laboratory for Recombiant Pharmaceutical Protein expression System of Henan, School of Basic Medicine, Xinxiang Medical University, Xinxiang, 453003, Henan; ⁴Medical College of Dalian University, Dalian 116622, Liaoning Province, China.

For correspondence:- Changgao Jiang Email: jch2011@163.com Tel:+864332660355

Accepted: 15 November 2020 Published: 29 December 2020

Citation: Han LZ, Jiang C, Mi C, Wang KS, Zuo HX, Wang Z, et al. Excisanin A suppresses proliferation by inhibiting hypoxia-inducible factor-1? expression in human hepatocellular carcinoma cells. Trop J Pharm Res 2020; 19(12):2483-2489 doi: 10.4314/tjpr.v19i12.1

© 2020 The authors.
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Abstract

Purpose: To investigate the effect of excisanin A on human hepatocellular carcinoma cells as well as to elucidate its mechanism of action.

Methods: Molecular docking was used to determine the binding characteristics of excisanin A to HIF-1α protein. The transcriptional activation and viability of excisanin A were assessed using Luciferase reporter and MTT assay. The HIF-1α protein in the nucleus was assayed using western blot and immunofluorescence. HIF-1α and VEGF mRNA levels were evaluated using reverse-transcription polymerase chain reaction (RT-PCR). Cell proliferation was determined by flow cytometry, as well as by EdU and clonogenic assays. In vivo tumor growth was assessed in a murine xenograft model of SK-Hep1 cells.

Results: Excisanin A inhibited HIF-1α transcriptional activation, as well as HIF-1α protein synthesis (p < 0.001). Excisanin A also reduced VEGF protein and mRNA expressions (p < 0.001). In addition, the compound inhibited the proliferation of hepatocellular carcinoma cells. and tumor growth in the xenograft tumor model.

Conclusion: Excisanin A is a potent HIF-1α inhibitor, supporting its potential development for human hepatoma therapy.

Keywords: Excisanin A, HIF-1?, Protein synthesis, Hepatoma therapy