J Cancer 2020; 11(7):1679-1692. doi:10.7150/jca.38624 This issue

Research Paper

Curcumol inhibits the proliferation and metastasis of melanoma via the miR-152-3p/PI3K/AKT and ERK/NF-κB signaling pathways

Ning Ning1#, Sulai Liu1,4,5#, Xiehong Liu1,3, Zeyu Tian1, Yu Jiang1,3, Nanhui Yu1,3, Boyu Tan1, Hao Feng1, Xing Feng2✉, Lianhong Zou1,3✉

1. First Affiliated Hospital of Hunan Normal University (Hunan Provincial People's Hospital), Changsha, Hunan, China
2. Key Laboratory of Study and Discovery of Small Targeted Molecules of Hunan Province, School of Medicine, Hunan Normal University, Changsha, Hunan, China
3. Hunan Provincial Institute of Emergency Medicine, Hunan Provincial Key Laboratory of Emergency and Critical Care Metabonomics, Changsha, Hunan, China
4. Department of Hepatobiliary Surgery, Hunan Provincial People's Hospital, Changsha, Hunan, China
5. Hunan Research Center of Biliary Disease, Changsha, Hunan, China.
#These authors contributed equally to this work.

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Citation:
Ning N, Liu S, Liu X, Tian Z, Jiang Y, Yu N, Tan B, Feng H, Feng X, Zou L. Curcumol inhibits the proliferation and metastasis of melanoma via the miR-152-3p/PI3K/AKT and ERK/NF-κB signaling pathways. J Cancer 2020; 11(7):1679-1692. doi:10.7150/jca.38624. Available from https://www.jcancer.org/v11p1679.htm

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Abstract

Melanoma is the most aggressive and treatment-resistant form of skin cancer. Curcumol is a Chinese medicinal herb traditionally used as a cancer remedy. However, the molecular mechanisms underlying the anticancer activity of curcumol in melanoma remains largely unknown. In the present study, we observed that Curcumol decreased mouse melanoma B16 cell proliferation and migration. The xenograft tumor assay showed that curcumol reduced melanoma volume and lung metastasis. Curcumol upregulated the expression of E-cadherin and downregulated the expression of N-cadherin, MMP2 and MMP9 in mouse melanoma B16 cell. Western blot analysis revealed that curcumol reduced the translocation of p65 to the nucleus and decreased p-ERK. Furthermore, curcumol attenuated c-MET, P13K and p-AKT protein expression and upregulated miR-152-3p gene expression. The dual-luciferase reporter assay indicated that c-MET was a target gene of miR-152-3p. Reduced expression of miR-152-3p partially attenuated the effect of curcumol on mouse melanoma B16 cell proliferation and migration. The decrease in c-MET, P13K and p-AKT protein expression following curcumol treatment in mouse melanoma B16 cells was notably attenuated by the miR-152-3p inhibitor. Taken together, our findings suggested that curcumol attenuated melanoma progression and concomitantly suppressed ERK/NF-κB signaling and promoted miR-152-3p expression to inactivate the c-MET/PI3K/AKT signaling pathway.

Keywords: Curcumol, Melanoma, miR-152-3p, c-MET/PI3K/AKT signaling pathway, ERK/NF-κB signaling pathway