In vitro cytotoxic activities of selected Saudi medicinal plants against human malignant melanoma cells (A375) and the isolation of their active principles

Introduction: Natural products are known to be a continuous source of potential anti-cancer agents due to their chemical and biological diversity. This study aimed to evaluate the in vitro cytotoxic properties of medicinal plants and their mechanisms of action in human malignant melanoma cells. Methodology: The study investigated the effect of the cytotoxic extracts on cell cycle, caspase-3/7, apoptosis induction using Annexin V-FITC/PI staining, morphological changes and lactate dehydrogenase activity and 2D cell migration studies. Results: There were 9 extracts considered to be promising (GI50 < 30 µg/mL); Haplophyllum tuberculatum (0.45 µg/mL), Plicosepalus curviflorus (4 µg/mL), Capparis decidua (10 µg/mL), Acacia nilotica (11 µg/mL), Aizoon canariense (14 µg/mL), Carissa edulis (15 µg/mL), Pulicaria schimperi (19 µg/mL) Cyperus rotundus (20 µg/mL), Osteospermum vaillantii (21 µg/mL). Cell cycle arrest at S phase was detected in cells treated with C. decidua, C. edulis, H. tuberculatum, P. curviflorus and P. schimperi. Cellular exposure to A. canariense resulted in G2/M arrest whereas A. nilotica, C. rotundus and O. vaillantii elevated the sub-G1 population. Caspase-3/7 was activated by C. decidua, C. edulis, C. rotundus, H. tuberculatum, P. schimperi and O. vaillantii. Most of the cytotoxic effects were accompanied by externalization of phosphatidylserine and morphological abnormalities like cell shrinkage and chromatin condensation. Lupeol was isolated from C. decidua, justicidin A, B, tuberculatin and tuberculatin acetate from H. tuberculatum and ursolic acid and its acetate from C. edulis as the anti-melanoma principles. Conclusion: The bio-guided isolation of plants extracts led to the identifications of anti-melanoma constituents belonging to different classes including lignans, lignan glycosides, triterpenes and flavonoids