Galloyl-RGD induces oxidative stress-mediated apoptosis in human melanoma cells

Melanoma is a malignant tumor arising from melanocytes and is characterized by rapid metastasis, making it the most aggressive form of skin cancer. Galloyl-RGD is a novel compound that combines gallic acid with RGD (Arg-Gly-Asp) tripeptide motif to overcome the problems associated with gallic acid, such as instability at high temperatures and low solubility. Although Galloyl-RGD has been previously investigated for its biological stability, regulation of melanin production, and anti-photoaging effects, its potential anticancer activity has not been clearly elucidated. In this study, proteomic profiling using two-dimensional electrophoresis and peptide mass fingerprinting suggested that Galloyl-RGD may influence melanoma cell survival and potentially trigger apoptosis-related pathways in SK-MEL28 cells. To validate these findings, we performed functional assays to evaluate the effects of Galloyl-RGD on cell viability, cell cycle progression, migration, and apoptosis in SK-MEL28 cells. Galloyl-RGD significantly reduced cell viability in SK-MEL28 melanoma cells in a dose- and time-dependent manner. It induced both early and late apoptosis and increased G1 phase arrest while reducing progression to the S and G2/M phases. Galloyl-RGD treatment elevated intracellular reactive oxygen species (ROS) levels, accompanied by activation of the stress-responsive JNK and p38 MAPK signaling pathways. In addition, the expression of key regulators associated with cell cycle progression and cell survival, including Cyclin D1, AKT/NF-κB, and Bcl-2, was markedly suppressed. Collectively, these findings demonstrate that Galloyl-RGD induces oxidative stress and modulates key survival and apoptotic signaling pathways in melanoma cells, suggesting its potential as a candidate compound targeting stress-associated mechanisms in melanoma.