The Anticancer Effect of Inula viscosa Methanol Extract by miRNAs’ Re-regulation: An in vitro Study on Human Malignant Melanoma Cells

Abstract

Alternative and natural therapies are needed for malignant melanoma (MM), the most deadly skin cancer type due to chemotherapy’s limited effect. In the present study, we evaluated the anticancer potentials of Inula viscosa methanol and water extracts (IVM and IVW) on MM cells, A2058 and MeWo, and normal fibroblasts. After the chromatographic and antioxidant activity analysis, their antiproliferative effects were determined with the increasing doses for 24-72 h. IVM induced more cell death in a dose and time-dependent manner in MM cells compared to IVW. This effect was probably due to the higher amount of phenolics in it. IVM significantly induced more apoptotic death in MM cells than fibroblasts (p < 0.01), which was also supported morphologically. IVM also caused cell cycle arrest at G0/G1 and G2/M phases in A2058 and MeWo, respectively, and suppressed the migration ability of MM cells (p < 0.01). Additionally, IVM was found to have significant potential in regulating MM-related miRNAs, upregulating miR-579 and miR-524, and downregulating miR-191 and miR-193, in MM cells (p < 0.05, p < 0.01). As a result, the anticancer effect of IVM via regulating miRNAs’ expression has been demonstrated for the first time. Thus, IVM, with these potentials, may be a promising candidate for MM treatment.

Acknowledgments

We thank Rıfat Okuyanlar, who sent us fresh Inula viscosa from the Agean part of Turkey. We also thank Dr. Seyhan Türk and Dr. Nalan Yıldız, who kindly provided cancer cell lines for this study.

Disclosure Statement

No potential conflict of interest was reported by the authors.

Authorship Contributions

Concept and design: D.K.C., Ü.E., I.E.E.; Data collection or processing: D.K.C., I.E.E., O.A., H.M.; Analysis or interpretation: D.K.C., I.E.E., Ü.E., O.A.; Literature Search: D.K.C., I.E.E., Ü.E., Drafting the article or revising: D.K.C., Ü.E., I.E.E.; Final approval of the manuscript: D.K.C., Ü.E., G.C., B.T.

Additional information

Funding

This study was supported by a grant from the Scientific Research Projects Foundation of the Bursa Uludag University, Bursa, Turkey [Project No. KUAP(T)-2018/18].