Novel anticancer mechanisms of melanin: Effects on cancer cell adhesion, survival, and migration

Melanoma is the deadliest form of skin cancer, with 330,000 new cases diagnosed and 60,000 deaths globally each year. While early-stage melanoma is often treatable, metastatic melanoma usually has poor prognosis with a high mortality rate. Melanin, a pigment synthesized through the melanogenesis pathway, has been reported to exert anti-cancer effects. However, the molecular mechanisms underlying its protective role remain poorly understood. We hypothesize that melanin may exert anticancer activity by reducing cancer cell survival and suppressing metastatic potential. This study uses 3 different cancer cell lines, including U937 (monocytic), HTB-11 (neuronal), and Colo320 (colorectal), and utilizes a combination of methods, including in silico molecular docking, cell attachment assays, and MTT assays, to evaluate the effects of melanin on cancer cell adhesion, proliferation, and survival. The results revealed that melanin decreased U937 (monocytic) cancer cell adhesion in a dose dependent manner: at a lower concentration, melanin increased cell adhesion by 29.5%, while in a higher concentration, it decreased cell adhesion. In HTB-11 cells, high concentration of melanin decreased cell proliferation by 48.61%, while in Colo320 cells, low concentration of melanin significantly suppressed cell growth by 63%. Data also showed that melanin has a strong binding affinity to cancer-related target proteins, including MMP2, MMP9, CDH1, and ITGB1, the possible molecular and genetic mechanisms of melanin in working with known cancer target proteins to regulate cancer growth. In conclusion, these findings suggest novel molecular pathways by which melanin may regulate cancer cell survival, adhesion, and migration. Collectively, this study provides new evidence for melanin as a potential anticancer agent with differential, dose-dependent effects, underscoring its relevance as a therapeutic lead for targeting diverse cancer types. D.L. is with Manhasset Secondary School, Manhasset, NY, USA. W.Z. is with SCI research institute, Jericho, NY, USA