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

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.

Chlorogenic acid induces apoptosis, inhibits metastasis and improves antitumor immunity in breast cancer via the NF‑κB signaling pathway

“…It has been revealed that microRNA (miR)-1224-5p inhibited metastasis and EMT in colorectal cancer by targeting the SP1-mediated NF-κB signaling pathways ( 41 ). In addition, curcumol could inhibit the proliferation and metastasis of melanoma via the miR-152-3p/PI3K/AKT and ERK/NF-κB signaling pathways ( 42 ). In the present study, mechanism analysis via western blotting demonstrated that CGA significantly downregulated the expression levels of NF-κB-associated proteins and EMT process-associated proteins, indicating that CGA impaired NF-κB, and then inhibited the EMT signaling pathway, thereby suppressing breast cancer cell migration and invasion.…”

MicroRNA-21 Contributes to Cutaneous Squamous Cell Carcinoma Progression via Mediating TIMP3/PI3K/AKT Signaling Axis

“…The activated PI3K/AKT pathway has been mentioned in skin cancer carcinogenesis, 26 and the PI3K/AKT pathway deficit can partially attenuate melanoma progression. 27 Moreover, the PI3K/AKT/mTOR pathway was displayed by Nardo et al to play an indispensable role in the pathogenesis of CSCC. 14 A recent study indicated that miR-21 directly targets and inhibits the expression of PTEN (a negative modulator of the PI3K/AKT pathway), and miR-21 inhibition upregulated PTEN expression but impaired the PI3K/AKT pathway, thereby elevating liver cancer cell apoptosis.…”

Long non‑coding RNA TTN‑AS1 regulates the proliferation, invasion and migration of triple‑negative breast cancer by targeting miR‑211‑5p

“…The present study demonstrated that TTN-AS1 knockdown inhibited the invasive and migratory abilities of both MDA-MB-453 and MDA-MB-231 cells, which was reversed by transfection with the miR-211-5p inhibitor. MMPs, including MMP-2 and MMP-9, are major components that are implicated in invasion and migration, and the upregulation of these proteins is closely associated with the aggressiveness and metastasis of TNBC ( 32 – 34 ). In the present study, decreased MMP-2 and MMP-9 expression was observed following TTN-AS1 knockdown, which was reversed following transfection with the miR-211-5p inhibitor.…”