Abstract Melanoma is a highly aggressive cancer, primarily due to its tendency to metastasize, recur, and develop resistance to standard chemotherapy. (2 Methyl-Butyryl) Shikonin (BSHK), a natural pigment derived from naphthoquinone, has been explored as a potential anti-cancer agent due to its ability to suppress the growth and proliferation of various cancer cells and inhibition of tyrosinase enzyme activity Dacarbazine a chemotherapy drug is widely used to treat several cancers, including melanoma. However, melanoma treatment failure often occurs due to acquired resistance, leading to metastasis and relapse. Current study aimed to determine if BSHK could enhance the sensitivity of melanoma cells towards chemotherapeutic drug dacarbazine and to explore the molecular mechanisms underlying with it. Biological effects were examined using MTT assay, Annexin-V/FITC and Immuno-blotting Assays. These findings revealed that BSHK significantly enhanced the cell growth inhibition potential of dacarbazine against melanoma cells . The combination of BSHK and dacarbazine increased ROS production and triggered higher rates of cell apoptosis. Importantly, the combined treatment downregulated MITF and Bcl-2 levels and upregulated BAX, Caspase 3 levels in melanoma cells. In conclusion, (2-Methylbutyryl) Shikonin sensitizes melanoma cells to dacarbazine by inhibiting melanogensis thereby increasing their susceptibility to apoptosis. The synergistic anticancer effects of (2-Methylbutyryl) Shikonin and dacarbazine suggest that their combination could be a promising therapeutic strategy for treating melanoma Citation Format: Aalim Maqsood. Bhat, Sheikh Tasduq. Abdullah. A naturally occurring naphthoquinone, (2-methylbutyryl) shikonin, potentiates dacarbazine anti-melanoma efficacy through melanogenesis inhibition and ROS-mediated apoptosis abstract. In: Proceedings of the 18th AACR Conference on the Science of Cancer Health Disparities; 2025 Sep 18-21; Baltimore, MD. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2025;34(9 Suppl):Abstract nr B128.
Bhat et al. (Thu,) studied this question.