Complex Inhibitory\nActivity of Pentacyclic Triterpenoids\nagainst Cutaneous Melanoma In Vitro and In Vivo: A Literature Review\nand Reconstruction of Their Melanoma-Related Protein Interactome

Pentacyclic triterpenoids (PTs) are a class of plant\nmetabolites\nwith a wide range of pharmacological activities, including strong\nantitumor potential against skin malignancies. By acting on multiple\nsignaling pathways that control key cellular processes, PTs are able\nto exert complex effects on melanoma progression in vitro and in vivo.\nIn this review, we have analyzed the works published in the past decade\nand devoted to the effects of PTs, both natural and semisynthetic,\non cutaneous melanoma pathogenesis, including not only their direct\naction on melanoma cells but also their influence on the tumor microenvironment\nand abberant melanogenesis, often associated with melanoma aggressiveness.\nSpecial attention will be paid to the molecular basis of the pronounced\nantimelanoma potency of PTs, including a detailed consideration of\nthe pathways sensitive to PTs in melanoma cells, as well as the reconstruction\nof the melanoma-related protein interactome of PTs using a network\npharmacology approach based on previously published experimentally\nverified protein targets of PTs. The information collected on the\nprimary targets of PTs was compiled in the Protein Interactome of\nPTs (PIPTs) database, freely available at http://www.pipts-db.ru/, which\ncan be used to further optimize the mechanistic studies of PTs in\nthe context of melanoma and other malignancies. By summarizing recent\nresearch findings, this review provides valuable information to scientists\nworking in the fields related to the evaluation of melanoma pathogenesis\nand development of PTs-based drug candidates.