A comprehensive and systematic review on Curcumin as a promising candidate for the inhibition of melanoma growth: From pre-clinical evidence to molecular mechanisms of action

Background: Melanoma, a highly malignant skin tumor, can develop systemic metastases during the early stage. Several studies of melanoma animal models indicate that curcumin, a natural plant extract, inhibits melanoma growth through various mechanisms. To evaluate the relationships among different experimental conditions, curcumin itself, its derivatives, and special formulations, it is necessary to conduct a systematic review and meta-analysis.

Purpose: This meta-analysis aims to evaluate the potential of Curcumin as a drug for inhibiting the growth of melanoma and to determine the optimal dosage range and treatment duration for Curcumin administration.

Methods: A systematic search of studies published from inception to December 2023 was conducted across six databases (PubMed, Web of Science, Embase, China National Knowledge Infrastructure, Wanfang Data, and VIP). Methodological quality was assessed using SYRCLE's RoB tool. Study heterogeneity was assessed using Cochran's Q test and I² statistics. Publication bias risk was evaluated using a funnel plot. All analyses were performed using R (version 4.3.3). Additionally, three-dimensional effect analysis and machine learning techniques were utilized to determine the optimal dosage range and treatment duration for Curcumin administration.

Results: Forty studies involving 989 animals were included. The results demonstrated that, relative to the control group, administration of Curcumin resulted in a significant reduction in tumor volume. [SMD=-3.44; 95 % CI (-4.25, -2.63); P<0.01; I² = 79 %] and tumor weight [SMD=-1.93; 95 % CI (-2.41, -1.45); P<0.01; I² = 75 %]. Additionally, Curcumin demonstrated a significant capacity to decrease the number of lung tumor nodules and microangiogenesis, as well as to extend survival time, in animal models. The results from three-dimensional effect analysis and machine learning emphasize that the optimal dosage range for Curcumin is 25-50 mg/kg, with an intervention duration of 10-20 days.

Conclusion: Curcumin can inhibit the growth of melanoma, and the dose-response relationship is not linear. However, further large-scale animal and clinical studies are required to confirm these conclusions.