Complex Inhibitory Activity of Pentacyclic Triterpenoids against Cutaneous Melanoma In Vitro and In Vivo: A Literature Review and Reconstruction of Their Melanoma-Related Protein Interactome.

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