BackgroundThe Wnt pathway is a major pathway in the pathogenesis of skin cancer. Moreover, crocin is one of the carotenoid compounds present in the flowers of gardenia and crocus. Crocin is responsible for the characteristic color of saffron.AimsThis study was conducted to discover the therapeutic effects of crocin against skin cancer induced in mice by blocking the Wnt pathway with subsequent effects on inflammation and fibrosis.MethodsFor the induction of skin cancer in mice, the application of DMBA and Croton oil was used. The dorsal skin was used for the evaluation of the gene and protein expression of TGF-β, SMAD, Wnt, β-catenin, TNF-α, and NFκB. Part of the skin is stained with Mallory trichrome.ResultsThe use of crocin for treating skin cancer mice significantly reduced both the number of tumors and the number of scratches. In addition, crocin inhibited epidermal hyperplasia. Finally, crocin reduced the gene expression and protein levels of Wnt, β-catenin, SMAD, NFκB; TGF-β and TNF-α.ConclusionsCrocin produced therapeutic effects against skin cancer induced in mice by blocking the expression of Wnt followed by blocking the pro-inflammatory pathway through downregulation of NFκB and TNF-α. In addition, crocin blocked the fibrosis pathway via the downregulation of TGF-β.