Chrysophanol induces cell apoptosis and suppresses cell invasion by regulating AKT and MAPK signaling pathway in melanoma cells

Melanoma is a highly heterogeneous and invasive tumor with poor prognosis due to its resistance to radiotherapy, chemotherapy, and immunotherapy. Chrysophanol has the anti-carcinogenic role in a variety of tumors. Although the anti-proliferative role of chrysophanol in melanoma has been reported, its specific molecular mechanisms are still unclear. In the present study, the proliferation, migration, invasion, apoptosis, and cell cycle of A375 and A2058 cells were evaluated through MTT, colony formation, cell scratch, Transwell, and flow cytometry assays. Besides, the relative levels of proteins related to AKT and MAPK signaling pathway were determined by western blotting. The results revealed that chrysophanol significantly inhibited cell viability, colony formation, and cell invasive but increased the relative wound width of A375 and A2058 cells. Chrysophanol also notably enhanced the apoptotic rate, accompanied with the induced protein levels of Bax and Cleaved caspase-3 and reduced protein level of Bcl-2. In addition, chrysophanol observably promoted the ratio of G0/G1 phase, while restrained the relative protein expressions of Cyclin D1 and CDK4. Furthermore, the relative expressions of p-AKT/AKT, p-ERK1/2/ERK1/2, and p-JNK/JNK were significantly decreased, and the relative expression of p-38/38 was enhanced by 20, 50, and 100 ??M chrysophanol treatment. Totally, the dose-dependent effects of chrysophanol on melanoma cell proliferation, migration, invasion, apoptosis, and cell cycle were observed. To sum up, these results revealed that chrysophanol induced cell apoptosis and suppressed cell invasion by regulating AKT and MAPK signaling pathway in both A375 and A2058 cells in a dose -dependent manner.