Chemical and Biological Characterization of the Anticancer Potency of Salvia fruticosa in a Model of Human Malignant Melanoma

Abstract

Malignant melanoma is one of the most aggressive types of skin cancer with an increasing incidence worldwide. Thus, the development of innovative therapeutic approaches is of great importance. Salvia fruticosa (SF) is known for its anticancer properties and in this context, we aimed to investigate its potential anti-melanoma activity in an in vitro model of human malignant melanoma. Cytotoxicity was assessed through a colorimetric-based sulforhodamine-B (SRB) assay in primary malignant melanoma (A375), non-malignant melanoma epidermoid carcinoma (A431) and non-tumorigenic melanocyte neighbouring keratinocyte (HaCaT) cells. Among eight (8) different fractions of S. fruticosa extracts (SF1-SF8) tested, SF3 was found to possess significant cytotoxic activity against A375 cells, while A431 and HaCaT cells remained relatively resistant or exerted no cytotoxicity, respectively. In addition, the total phenolic (Folin–Ciocalteu assay) and total flavonoid content of SF extracts was estimated, whereas the antioxidant capacity was measured via the inhibition of tert-butyl hydroperoxide-induced lipid peroxidation and protein oxidation levels. Finally, apoptotic cell death was assessed by utilizing a commercially available kit for the activation of caspases - 3, - 8 and - 9. In conclusion, the anti-melanoma properties of SF3 involve the induction of both extrinsic and intrinsic apoptotic pathway(s), as evidenced by the increased activity levels of caspases - 8, and - 9, respectively.

Comparative Evaluation of Anticancer Activity of Natural Methoxylated Flavones Xanthomicrol and Eupatilin in A375 Skin Melanoma Cells

“…Firstly, the XAN and EUP cytotoxic activity was explored in A375 cells, a tumor cell line previously used to investigate the cytotoxicity of natural flavonoids [ 39 , 43 ]. The values of viability (expressed as % of the control) induced by 24 h-treatment with different concentrations (from 2.5 to 200 μM) of EUP and XAN in melanoma A375 cells by the MTT cell viability assay are reported in Figure 2 .…”

“…Melanoma is a skin cancer caused by the malignant transformation of melanocytes [ 38 ]. Cutaneous melanoma represents the most aggressive and deadliest type of skin cancer (accounting for 5% of total skin cancers), with an increasing incidence worldwide [ 39 , 40 , 41 ]. It is one of the most therapy-resistant types of cancer [ 38 ]; therefore, the development of new therapeutic approaches is strongly mandatory.…”

“…In this study, we explored the ability of EUP and XAN to affect cell lipid metabolism, as another possible anticancer mechanism, in human diploid immortalized skin malignant melanoma (A375) cells, a tumor cell line amply used to assess the anticancer properties of compounds/extracts from natural sources in cutaneous melanoma [ 39 , 43 ]. Changes in the cell profile of phospholipids (PL), free cholesterol (FC), and total fatty acids (TFA) were examined in A375 melanoma cells after 24 h of incubation with EUP and XAN.…”

Phytochemical Profile and Anticancer Activity from Medicinal Plants Against Melanoma Skin Cancer: A Review

“…In addition, it induces apoptosis by activating the extrinsic apoptotic pathway through Caspase-8 activation. It also involves an intrinsic apoptotic pathway through caspase-9 activation (Kyriakou et al, 2021). Especially in melanoma cells, previous studies have shown that CA seems to block cell migration of B16F10, an aggressive melanoma cell line, by inhibiting epithelialmesenchymal transition (EMT).…”

Chemical Profiling and Antioxidant and Anti-Amyloid Capacities of Salvia fruticosa Extracts from Greece

“…Salvia fruticosa Miller (SF), frequently cited as Greek sage, is an indigenous plant species of the eastern Mediterranean that belongs to the Lamiaceae family [ 7 ]. SF has shown various medicinal properties, such as anticancer [ 8 ], antibacterial [ 9 ], antiparasitic [ 10 ], antioxidant [ 11 ], hypoglycemic [ 12 ], anti-inflammatory [ 13 ], antiglycative [ 14 ], anticholinesterase [ 15 ], and neuroprotective [ 16 , 17 ]. Furthermore, it has been used as an herbal remedy throughout the Mediterranean countries to resolve a plethora of conditions, such as stomach ache, indigestion [ 18 ], diabetes [ 19 ], colds [ 20 ], depression, gingivitis, constipation, dysmenorrhea, hypotension [ 21 ], and diarrhea [ 22 ].…”