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.
Highlights
Skin cancer is one of the most frequent types of cancer, with increasing rates of incidence and mortality worldwide [1,2,3,4]
Our results indicated that SF3 was the richest extract fraction in the context of having the highest Total Phenolic Content (TPC) (319.188 μg of gallic acid equivalents (GAE)/g of extract) and Total Flavonoid Content (TFC)
Our results indicated that the activity levels of Caspase - 8 were significantly increased (2000–3000 relative fluorescence units (RFU)
Summary
Skin cancer is one of the most frequent types of cancer, with increasing rates of incidence and mortality worldwide [1,2,3,4]. Mortality rates remain high despite the development and improvement of therapeutic approaches. To this end, chemoprevention, utilizing synthetic and/or naturally derived agents, has emerged as a promising and alternative approach against cancer management, including MM [7,8,9]. S. fruticosa (SF) is an endemic plant mainly found in the Mediterranean and Irano-Turanian regions It is known as Greek sage, and has been reported to exert significant antioxidant and anticancer activity, possibly due to the presence of phenolic compounds (e.g., Rosmarinic acid; RA) that are well known for their antioxidant and antitumor effects [11,12,13,14]. The treatment of melanoma cell lines with CA resulted in: (i) induction of apoptotic cell death; (ii) inhibition of epithelial-to-mesenchymal transition (EMT) and metastasis; as well as (iii) improvement of the cytotoxicity profile of several anticancer drugs [16,17]
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