Figure 7: A schematic depiction of a plausible role of zinc in melanoma progression.

Marginal parts of tumour border with a reactive zone of an adjacent healthy tissue. In these parts of melanoma, frequent necroses, a presence of H₂O₂ and elevation of malondialdehyde (MDA) can be found. (A) High zinc in marginal sections of melanoma may indicate a physiological defence of zinc-containing antioxidant molecules against the potential danger of ongoing oxidative stress. Although intralesional regions of melanomas generally exhibit hypozincemia status, oxidative stress in reactive zones/marginal parts interface can likely result in an oxidative stress-triggered transport of zinc-containing antioxidant molecules from adjacent healthy tissue and temporary accumulation of zinc. (B) Physiologically, an expression of melanosomes is regulated by microphthalmia-associated transcription factor gene (MITF) and phosphorylation (P) of the homonymous MITF-encoded protein (Mitf). (C) Translated melanosomes are the place for entire melanin synthesis, starting by action of tyrosinase, producing L-3,4-dihydroxyphenylalanine (DOPA) from tyrosine (Tyr). Tyrosinase further produces DOPA quinone from DOPA. DOPA quinone can be converted through a sequence of reactions to various types of melanins (black and brown eumelanins or red to yellow pheomelanin). (D) Noteworthy, another plausible reason for the free radicals formation in melanoma is a presence of abnormal and incomplete melanosomes, causing a significant leakage of the reactive melanin prescursors, causing oxidative stress in the pigmented tumours through redox cycling and an accumulation of zinc ions originating from antioxidant molecules from adjacent tissues as a kind of physiological protection.