Hinokiflavone induces apoptosis in melanoma cells through the ROS-mitochondrial apoptotic pathway and impairs cell migration and invasion

Melanoma, the highest degree of malignancy, is one of the most common skin tumors. However, there is no effective strategy to treat melanoma in current clinical practice. Therefore, it is urgent to find an efficient drug to overcome melanoma. Here, the in vitro anticancer effects of a natural product named hinokiflavone on three melanoma carcinoma cell lines (human melanoma A375 and CHL-1 cells, murine melanoma B16-F10 cells) and mechanisms of action were explored. The results of MTT assay revealed that hinokiflavone inhibited cell proliferation of these cell lines in a dose- and time-dependent manner. Interestingly, hinokiflavone showed low toxicity to normal liver cells. Flow cytometry assay and EdU incorporation assay indicated that hinokiflavone affected A375 and B16 cells survival by inducing apoptosis and blocking cell cycle progression at S phase in a concentration-dependent manner. Moreover, hinokiflavone enhanced the reactive oxygen species (ROS) and decreased the mitochondrial membrane potential obviously. Furthermore, hinokiflavone effectively impaired A375 cells migration and invasion, and down-regulated the expression of matrix metalloproteinase (MMP) MMP2 and MMP9. The above-mentioned results demonstrated that hinokiflavone could be a novel chemotherapeutic agent in melanoma treatment by inhibiting cell proliferation, inducing apoptosis and cell cycle arresting and blocking cell migration and invasion.