Humic and Fulvic Acids Induced Thermodynamic and Structural Instability of Tyrosinase With Antiproliferative Effect on A375 Melanoma Cancer Cell Line

Background: The tyrosinase enzyme catalysis monophenols to melanin pigments through the melanogenesis process. For this reason, various inhibitors have been studied for enzyme regulations in melanogenesis abnormalities in both the food and cosmetics industries. In this study, the effect of humic acid (Hu) and fulvic acid (Fu) on the structure, activity, and stability of mushroom tyrosinase (MT) was investigated. Methods: These two organic acids are the main components of soil humus. Assessment of the thermodynamic and structural stability of enzymes was obtained through thechemical and thermal denaturations and (8-anilino-naphthalene sulfonic acid) ANS fluorescence analysis. The Hu and Fu impact on A375 melanoma cancer cell viability was achieved by MTT assay.   Findings: The results of enzyme half denaturation concentration (Cm), melting points (Tm), ΔG0 values and external fluorescence emissions in the presence of Hu and FA proved the reduction of the thermodynamic and structural stability of MT by these compounds. The anti-proliferation effects of the compounds were confirmed by the inhibitory concentrations of 50% (IC50) of 31.5 and 42.7 µM and 12.5 and µM at time points of 24 and 48 hours treatments of the A375 melanoma cell line by Hu and Fu, respectively. Conclusion: Humic and fulvic acids can be expected to contribute to advancing skin disorder science play a crucial role in tyrosinase related disorders and anti-cancer effects, and good candidates for medical applications.