Licochalcone A restrains microphthalmia-associated transcription factor expression and growth by activating autophagy in melanoma cells via miR-142-3p/Rheb/mTOR pathway.
Phytother Res. 2019 Dec 2. Epub 2019 Dec 2. PMID: 31793097
Licochalcone A (LCA) was found to possess anticancer effects. This study aimed to investigate the anticancer effects and mechanisms of LCA in melanoma. A375 and B16 melanoma cells were stimulated with LCA, MTT assay was used to assess cell proliferation. Expression of miR-142-3p, microphthalmia-associated transcription factor (MITF, which regulates melanin production) and autophagy-related genes was determined by Real-time PCR or western blot. The apoptosis was analyzed by flow cytometry and caspase-3 activity. The roles of miR-142-3p and Ras homolog enriched in brain (Rheb) in LCA-affected cells were investigated by gain- and loss-of functions. LCA inhibited proliferation and MITF expression, but increased apoptosis and autophagy of melanoma cells. Moreover, LCA elevated miR-142-3p expression, but decreased its target gene Rheb expression. The effects of LCA on melanoma cells were abrogated by miR-142-3p inhibitor or Rheb overexpression. LCA suppressed mTOR signaling activation via Rheb. Additionally, rapamycin (a mTOR antagonist) notably attenuated the effects of Rheb on the autophagy, proliferation, apoptosis, and MITF expression in LCA-treated melanoma cells. In conclusion, LCA restrained MITF expression and growth by activating autophagy in melanoma cells via miR-142-3p/Rheb/mTOR pathway. This study suggested that LCA might be a potential therapeutic candidate for prevention and treatment of melanoma.