22β-hydroxytingenone induces apoptosis and suppresses invasiveness of melanoma cells by inhibiting MMP-9 activity and MAPK signaling

22β-hydroxytingenone (22-HTG) is a quinonemethide triterpene isolated from Salacia impressifolia (Miers) A. C. Smith (family Celastraceae), which has been used in traditional medicine to treat variety of diseases, including dengue, renal infections, rheumatism and cancer. However, the anticancer effects 22-HTG underlying molecular mechanisms melanoma cells have not yet elucidated. The present study investigated apoptosis induction antimetastatic potencial SK-MEL-28 human cells. First, vitro cytotoxic activity cultured cancer was evaluated. Then, cell viability determined using trypan blue assay (SK-MEL-28), followed by cycle, annexin V-FITC/propidium iodide assays (Annexin/PI), as well evaluate mitochondrial membrane potential, production reactive oxygen species (ROS) flow cytometry. Fluorescence microscopy acridine orange/ethidium bromide (AO/BE) staining also performed. RT-qPCR carried out expression BRAF, NRAS, KRAS genes. anti-invasiveness potential evaluated three-dimensional (3D) model reconstructed skin. reduced caused morphological changes, shrinkage, chromatin condensation, nuclear fragmentation. Furthermore, apoptosis, demonstrated increased with AO/BE Annexin/PI. may instability without involvement ROS production. KRAS, are important biomarkers development, treatment. In skin model, able decrease invasion capacity dermis. Our data indicate that anti-tumorigenic properties against through cycle arrest, inhibition invasiveness observed 3D model. As such, results provide new insights for future work on utilization malignant