Abstract:
Carrageenans, the polysaccharide from red algae, especially of the genera Chondrus, Eucheuma and Gigartina, are widely used in food, medicine and as an excipient in cosmetics and skincare products. Carrageenans have been shown to have prospective photoprotective effect against UVB irradiation on immortalised normal human keratinocyte (HaCaT) cells. The primary aim of this study was to assess the potential of iota (ι) and kappa (κ)-carrageenans and their combined effect with vitamin E on UVB-induced extracellular matrix (ECM) and cytoskeletal changes in HaCaT cells, and their antiproliferative and apoptotic effects on epidermoid carcinoma (A431NS) cells. The ECM degradation was assessed through the biological mediators epidermal growth factor receptor (EGFR), mitogen-activated protein kinase (MAPK), activating protein-1 (AP-1), and matrix metalloproteinases (MMPs) liberated by the UVB-induced cells. The antiproliferative effects on A431NS cells was evaluated based on the cytotoxicity profile, direct antiproliferation effect, DNA synthesis, translationally-controlled tumour protein (TPT1) gene expression and changes in the cytoskeleton structure. Carrageenans did not exhibit cytotoxicity at dosages <200 μg/ml in HaCaT cells. Cells pre-treated with carrageenans exhibited significantly (p<0.05) higher cell viability compared to the cells without treatment after UVB irradiation. Results also showed that the levels of the biological mediators significantly (p<0.05) reduced in carrageenan pre-treated cells, suggesting that carrageenans have the potential in maintaining the skin’s integrity by reducing the damage to ECM upon UVB exposure. The cytoskeletal structure in cells pre-treated with carrageenans were also more intact than the untreated cells. In addition, carrageenans enhanced the activities of the antioxidant enzymes superoxide dismutase (SOD) and catalase (CAT). The percentage of Rat Sarcoma (RAS)-Rapidly Accelerated Fibrosarcoma (RAF) gene mutation was also reduced in treated cells. When tested against epidermoid carcinoma (A431NS) cells, carrageenans exhibited cytotoxicity (CD50<100ug/ml) and antiproliferative effect in a concentration-dependent manner, inhibited DNA synthesis and downregulated the TPT1 gene expression. Also, the cytoskeleton structure was impaired after treatment. The presence of sulphur moieties, gelling effect, polysaccharide nature, vital minerals and ions is postulated to contribute to the photoprotective and anticancer potential of carrageenans. Taken together, the results suggest that carrageenans do possess photoprotective effects against UVB-induced toxicity and ECM damages, in addition to being a prospective anticancer agent. Apart from being just an excipient in cosmetics and skincare products, the presence of carrageenans potentially be of an added value as a photoprotective and anti-cancer agent if its photoprotective mechanism and anti-cancer potential can be established from this study.
