Lupan-Skeleton Pentacyclic Triterpenes with Activity against Skin Cancer: Preclinical Trials Evolution

Abstract

Skin cancer is an increasingly frequent pathology, with a dangerous high percentage of malignant melanoma. The use of synthetic chemotherapy raises the problem of severe adverse effects and the development of resistance to treatment. Therefore, the use of natural therapies became the focus of numerous research groups due to their high efficacy and lower systemic adverse effects. Among natural products evaluated as therapeutical agents against skin cancer, betulinic acid was emphasized as a highly selective anti-melanoma agent and is currently undergoing phase II clinical trials as topical application. Several other pentacyclic triterpenes exhibit antiproliferative activities. This chapter aims to present the latest main discoveries in the class of pentacyclic triterenes with antitumor effect and the evolution of their preclinical trials. Furthermore, it includes reports on plant sources containing pentacyclic triterpenes, as well as the main possibilities of their water solubilization and cancer cell targeting. A review on recent data regarding mechanisms of action at cellular and molecular levels complements information on the outstanding medicinal potential of these compounds.

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

“…According to various studies, BA, as well as BT molecules, fit best inside γ-cyclodextrin cavity as well as its derivative hydroxypropyl-γ-CD (HPGCD). BA water solubility increased 14 times when in complexes with HPGCD and this has also improved its antimelanoma activity as shown on the B16 cell line [4]. Soica et al [51] described BA activity in complexes with octakis-[6-deoxy-6-(2-sulfanylethanesulfone)]-γ-CD (GCDG) on metastatic and nonmetastatic B164A5 melanoma cell lines.…”

“…It is the most dangerous type of skin cancer due to its prominent metastasis and resistance to radio-and chemotherapy [3]. Changes in lifestyle, including exposure to excessive UV radiation, have led to a significant increase in the amount of melanoma incidence and melanoma-related deaths over the years; this accounts for 75% of skin cancer deaths [4,5]. Nowadays, standard melanoma treatment is mainly based on surgical procedures (at early stages), chemotherapy, radiation, immunotherapy and targeted therapies; nevertheless, effective treatment options in melanoma are still limited [3].…”

“…Nowadays, standard melanoma treatment is mainly based on surgical procedures (at early stages), chemotherapy, radiation, immunotherapy and targeted therapies; nevertheless, effective treatment options in melanoma are still limited [3]. Multi-drug resistance and severe side effects are the main drawbacks of chemotherapeutic agents used in skin cancer [4,6]. Thus, new therapies are still sought, and nature is considered to be a vast source of bioactive compounds with a potential antimelanoma effect.…”

“…They are known for their anti-inflammatory, analgesic, bactericidal, virostatic and hepatoprotective activity [8]. Moreover, many studies have confirmed their cytotoxic properties in vitro against various types of cancer [4], due to modulating the pathways that are involved in cell proliferation and apoptosis [9]. Some recent reviews on the general anticancer activity of triterpenoids have focused on the development of semi-synthetic derivatives [10][11][12] or on the efficacy of the most widely studied compound, betulinic acid (BA) [13][14][15][16][17], and also oleanolic acid (OA) [18].…”

Tetracyclic and Pentacyclic Triterpenes with High Therapeutic Efficiency in Wound Healing Approaches

“…Pentacyclic triterpenes, secondary metabolites extensively found in the plant kingdom, are located in various parts of the plant, such as the bark, root and leaves. An important number of studies showed the curative potential of lupane-type pentacyclic triterpenes (Figure 3) through various biological activities such as anti-inflammatory [28,29], anticancer [30,31], antioxidant [12], antiviral [13,32], antiparasitic [33] or healing properties [17], all of them being confirmed through extensive research.…”