Abstract
Malignant melanoma (MM) represents the most life-threatening skin cancer worldwide, with a narrow and inefficient chemotherapeutic arsenal available in advanced disease stages. Lupeol (LUP) is a triterpenoid-type phytochemical possessing a broad spectrum of pharmacological properties, including a potent anticancer effect against several neoplasms (e.g., colorectal, lung, and liver). However, its potential as an anti-melanoma agent has been investigated to a lesser extent. The current study focused on exploring the impact of LUP against two human MM cell lines (A375 and RPMI-7951) in terms of cell viability, confluence, morphology, cytoskeletal distribution, nuclear aspect, and migration. Additionally, the in ovo antiangiogenic effect has been also examined. The in vitro results indicated concentration-dependent and selective cytotoxicity against both MM cell lines, with estimated IC50 values of 66.59 ± 2.20 for A375, and 45.54 ± 1.48 for RPMI-7951, respectively, accompanied by a reduced cell confluence, apoptosis-specific nuclear features, reorganization of cytoskeletal components, and inhibited cell migration. In ovo, LUP interfered with the process of angiogenesis by reducing the formation of neovascularization. Despite the potential anti-melanoma effect illustrated in our in vitro-in ovo study, further investigations are required to elucidate the underlying LUP-induced effects in A375 and RPMI-7951 MM cells.
Highlights
Malignant melanoma (MM) is described as the tumor arising from the neoplastic transformation of melanin-producing cells—the melanocytes [1], and the leading cause of skin cancer-related deaths worldwide [2] despite its rareness [3]
The current study aims at providing an in vitro-in ovo insight into the anti-proliferative, anti-metastatic, and antiangiogenic properties of LUP as a potential chemotherapeutic agent in malignant melanoma management
The results indicated a dose-dependent cytotoxic activity of LUP on both cell lines (Figure 1A,B), the highest inhibition of the cell viability being recorded at the highest concentration tested (50 μM) when the percentages reached the values of 61.29% for A375 and 37.78% for RPMI-7951, respectively
Summary
Malignant melanoma (MM) is described as the tumor arising from the neoplastic transformation of melanin-producing cells—the melanocytes [1], and the leading cause of skin cancer-related deaths worldwide [2] despite its rareness [3]. Chemotherapy (e.g., dacarbazine) was the first-line option for advanced melanoma management [6,7,8], but due to severe adverse events, drug resistance, and lack of survival benefit, the treatment success rate has been considerably lowered [9,10,11]. The management of metastatic MM has significantly progressed with the emergence of targeted therapy and immune checkpoint inhibitors. Targeted therapy (e.g., vemurafenib, dabrafenib) has been associated with a high response rate, and with short-term therapeutic benefits and rapid development of tumor resistance (within several months). The treatment with immune checkpoint inhibitors (e.g., ipilimumab, pembrolizumab, nivolumab, atezolizumab) generates a superior overall survival among patients, but a lower response rate [11,12]. To overcome the current difficulties enquired in the treatment of advanced MM, improved therapeutic strategies are deeply required
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