Pharmaco-Toxicological Assessment of the Combined Cytotoxic Effects of Digoxin and Betulinic Acid in Melanoma Cells

• Published in: Life (Basel, Switzerland) Vol. 12; no. 11; p. 1855
• Main Authors: Rednic, Robert, Macasoi, Ioana, Pinzaru, Iulia, Dehelean, Cristina Adriana, Tomescu, Mirela-Cleopatra, Susan, Monica, Feier, Horea
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 01.11.2022; MDPI
• Subjects: Acids; Actin; Analysis; Anticancer properties; Antitumor activity; Apoptosis; Betulinic acid; Blood vessels; Cancer; Cancer therapies; Care and treatment; Cell death; Cell viability; Chorioallantoic membrane; Chromatin; Cytotoxicity; Digitalis; Digoxin; Drug synergism; Drug therapy; Eggs; Evaluation; F-actin fibers; Fibers; HET-CAM assay; Melanoma; melanoma cells; Morphology; Muscle proteins; Pharmacology, Experimental; Phytochemicals; Plant species; Reagents; Skin cancer; synergic effect; Testing; Triterpenes; Tumor cells; Canada; Romania; United States > US; Germany; digoxin; F-actin fibers; betulinic acid; synergic effect; melanoma cells; HET-CAM assay
• DOI: 10.3390/life12111855
• ISSN: 2075-1729

Betulinic acid, a small molecule from pentacyclic triterpenes class, has been widely studied for its antitumor activity, revealing that it induces the apoptosis of tumor cells in a selective manner. In recent years, digoxin, a cardiac glycoside found particularly in the plant species , has drawn interest for its potential antitumor properties. The present study was designed to evaluate the antimelanoma potential of betulinic acid (BA), digoxin (DG), and their association (DG + BA). In vitro assessments were performed 24 h post-treatment on two human melanoma cell lines (SK-Mel-28 and RPMI-7951). In addition, the potential irritant effects of the test samples were evaluated using the chorioallantoic membrane of hen's eggs. BA and DG exhibit a concentration-dependent cytotoxic activity, with the combination of the two having a more marked effect on the decrease in cell viability (~17% for SK-Mel-28 cells and ~23% for RPMI-7951 cells). Further, morphological changes (rounding of the cells and their separation from the plaque) and alterations in the nucleus and actin fibers (condensation of chromatin and actin fibers, formation of apoptotic bodies) were observed, indicating an apoptotic-like process. Moreover, no irritating effects were observed in ovo. As a result, DG + BA acid may have synergistic potential in the antitumor treatment of melanoma, but future studies are needed in order to clarify the biological mechanisms involved.