Progress in Antimelanoma Research of Natural Triterpenoids and Their Derivatives: Mechanisms of Action, Bioavailability Enhancement and Structure Modifications

Abstract

Melanoma is one of the most dangerous forms of skin cancer, characterized by early metastasis and rapid development. In search for effective treatment options, much attention is given to triterpenoids of plant origin, which are considered promising drug candidates due to their well described anticancer properties and relatively low toxicity. This paper comprehensively summarizes the antimelanoma potential of natural triterpenoids, that are also used as scaffolds for the development of more effective derivatives. These include betulin, betulinic acid, ursolic acid, maslinic acid, oleanolic acid, celastrol and lupeol. Some lesser-known triterpenoids that deserve attention in this context are 22β-hydroxytingenone, cucurbitacins, geoditin A and ganoderic acids. Recently described mechanisms of action are presented, together with the results of preclinical in vitro and in vivo studies, as well as the use of drug delivery systems and pharmaceutical technologies to improve the bioavailability of triterpenoids. This paper also reviews the most promising structural modifications, based on structure–activity observations. In conclusion, triterpenoids of plant origin and some of their semi-synthetic derivatives exert significant cytotoxic, antiproliferative and chemopreventive effects that can be beneficial for melanoma treatment. Recent data indicate that their poor solubility in water, and thus low bioavailability, can be overcome by complexing with cyclodextrins, or the use of nanoparticles and ethosomes, thus making these compounds promising antimelanoma drug candidates for further development.

The Anticancer Activities of Natural Terpenoids That Inhibit Both Melanoma and Non-Melanoma Skin Cancers

“…In another review, Wróblewska-Łuczka et al described anti-melanoma activities of 15 different terpenes with a focus on how these terpenes can be used as adjuvant therapy in melanoma treatment such as chemotherapy and immunotherapy [26]. Some lesser-known triterpenoids that have anti-melanoma effect have been described previously [27]. Along with other natural compounds, some terpenoids, including ingenol mebutate, glycyrrhizic acid, and botulin, are known to prevent NMSC [28].…”