Tropical Journal of Pharmaceutical Research

Original Research Article | OPEN ACCESS

Anethole suppresses the growth of human skin cancer cells by targeting microRNA498/STAT4 axis

Jiahang Li¹, Yingqiu Mao², Wei Li³

¹School of Clinical Medicine, Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan 611137, China; ²Institution of Traditional Medicine Research, Beijing University of Chinese Medicine, Beijing 100029, China; ³Department of Dermatology, Dongfang Hospital Beijing University of Chinese Medicine, Beijing 100078, China.

For correspondence:- Wei Li Email: liwei1909@gmail.com Tel:+8613134465438

Accepted: 31 October 2022 Published: 30 November 2022

Citation: Li J, Mao Y, Li W. Anethole suppresses the growth of human skin cancer cells by targeting microRNA498/STAT4 axis. Trop J Pharm Res 2022; 21(11):2391-2396 doi: 10.4314/tjpr.v21i11.18

© 2022 The authors.
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Abstract

Purpose: To investigate the effects of anethole on human skin cancer cells.

Methods: Cell viability was determined using CCK-8 and colony formation assay, while AO/EB and Annexin V/PI assays were used to assess apoptosis. The mRNA expressions of genes were assayed by quantitative reverse transcription-polymerase chain reaction (qRT-PCR).

Results: The growth of skin cancer cells was significantly reduced by anethole (p < 0.05). On the other hand, normal human skin cells were marginally affected by anethole. Furthermore, anethole significantly suppressed the colony formation potential of CRL-6475 skin cancer cells in a concentration-dependent manner (p < 0.05). Results from AO/EB and annexin V/PI staining assays revealed that anethole induced apoptosis in skin cancer cells, while qRT-PCR results indicate that anethole significantly up-regulated microRNA-498 in skin cancer cells (p < 0.05). However, anethole had no effect on the expression levels of miR-7, miR-9, miR-145, miR-31, miR-27, miR-498 miR-1298, miR-1299, 1179, miR-375, miR-508 and miR-23. CCK-8 assay results confirmed that miR-498 up-regulation significantly mimicked the anti-proliferative effects of anethole. Bioinformatics analysis and luciferase reporter assay led to identification of STAT4 as the regulatory target of miR-498. Furthermore, silencing of STAT4 significantly mimicked the effects of anethole administration (p < 0.05).

Conclusion: These results indicate that anethole inhibits skin cancer cell growth by targeting the miR-498/STAT4 axis, and therefore, has potentials for use in the management of skin cancer.

Keywords: Skin cancer, Melanoma, Metastasis, Anethole, Apoptosis, miR-498/STAT4 axis