The leading cause of death worldwide is
cancer. Many reports have proved the beneficial effect of mushrooms in
cancer. However, the precise mechanism is not completely clear. In the present study, we focused on the medicinal properties of biomolecules released by fairy ring-forming mushrooms. Fairy chemicals generally stimulate or inhibit the growth of surrounding vegetation. In the present study, we evaluated whether fairy chemicals (2-azahypoxanthine, 2-aza-8-oxohypoxanthine, and imidazole-4-carboxamide) exert anticancer activity by decreasing the expression of Axl and
immune checkpoint molecules in
melanoma cells. We used B16F10
melanoma cell lines and a
melanoma xenograft model in the experiments. Treatment of
melanoma xenograft with
cisplatin combined with
imidazole-4-carboxamide significantly decreased the
tumor volume compared to untreated mice or mice treated
cisplatin alone. In addition, mice treated with
cisplatin and
imidazole-4-carboxamide showed increased peritumoral infiltration of T cells compared to mice treated with
cisplatin alone. In vitro studies showed that all fairy chemicals, including
imidazole-4-carboxamide, inhibit the expression of
immune checkpoint molecules and Axl compared to controls.
Imidazole-4-carboxamide also significantly blocks the
cisplatin-induced upregulation of PD-L1. These observations point to the fairy chemical
imidazole-4-carboxamide as a promising coadjuvant
therapy with
cisplatin in patients with
cancer.