Tropical Journal of Pharmaceutical Research

Original Research Article | OPEN ACCESS

Irigenin exhibits anticancer activity against human colon cancer cells via autophagy, inhibition of cell migration and invasion, and targeting of ERK/MAPK signal pathway

Yan Zhan, Shuangxi Kong, Liang Fan, Jun Jiang

Department of Oncology, The Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030, China;

For correspondence:- Jun Jiang Email: hardyjiangjun77730@yahoo.com Tel:+862765696508

Accepted: 20 June 2021 Published: 29 July 2021

Citation: Zhan Y, Kong S, Fan L, Jiang J. Irigenin exhibits anticancer activity against human colon cancer cells via autophagy, inhibition of cell migration and invasion, and targeting of ERK/MAPK signal pathway. Trop J Pharm Res 2021; 20(7):1357-1363 doi: 10.4314/tjpr.v20i7.6

© 2021 The authors.
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Abstract

Purpose: To study the anticancer effect of naturally-occurring irigenin isoflavonoid on colon cancer, and to determine the mechanism involved.

Methods: The effect of irigenin on viability of normal and cancerous colon cells was assessed by MTT assay, while clonogenic assay was used to measure colony generation. Autophagy was examined by transmission electron microscopy (TEM) and western blotting. Transwell chamber assay was used to determine the influence of irigenin isoflavonoid on cell migration and invasion. The expression levels of ERK/MAPK signal pathway-associated proteins were assayed using Western blotting.

Results: Irigenin significantly decreased the viability of Caco-2 colon cancer cells, in contrast to normal CCD841 colon cells, and produced concentration-dependent anti-proliferative effects (p < 0.05). The number of cell colonies in control group decreased significantly (p < 0.05) upon exposure to irigenin. Results from TEM revealed that irigenin caused dose-dependent formation of autophagosomes, and dose-based up-regulation of the expressions of Beclin-1, LC3-I and LC3-II (p < 0.05). Moreover, irigenin markedly suppressed the migration and invasion of Coca-2 cells. Furthermore, irigenin exposure dose-dependently blocked the expressions of proteins associated with ERK/MAPK signal pathway in Coca-2 cells.

Conclusion: These results indicate that irigenin exerts potent inhibitory effect on the growth and migration of colon cancer cells. Furthermore, irigenin induces autophagy, inhibits cell migration and invasion, and targets ERK/MAPK survival signal pathway. Therefore, irigenin may be a lead candidate drug for colon cancer treatment. However, there is need for further in vivo and clinical studies to validate these findings.

Keywords: Colon cancer, Isoflavonoids, Irigenin, Autophagy, Cell migration, Cell invasion