MOLECULAR MECHANISMS OF PREVENTIVE AND THERAPEUTIC ACTIVITY OF THAI PLANT EXTRACTS IN SKIN CANCER

Abstract

Thai traditional medicine employs a wide range of indigenous herbs in the forms of tincture or tea for the cure of skin and systemic inflammatory diseases. UVB radiation is the most factors to induce skin damage, including skin cancer. The cutaneous squamous cell carcinoma (SCC) is the second most common form of non-melanoma skin cancer. The protection by Thai plants extracts against UVB DNA damage and cytotoxicity was investigated in human keratinocytes cell line HaCaT. High total phenolic and flavonoid contents were found in the ethanol and dichloromethane fractions. Dichloromethane extract of turmeric was shown to possess the highest antioxidant activity. The maximum UV absorptions were found in the ethanol extract of turmeric and in the dichloromethane extract of ginger. These extracts stimulated the synthesis of Thioredoxin 1, an antioxidant protein, and could protect human HaCaT keratinocytes from UV-induced DNA damage and cytotoxicity. In addition, In addition, the effect of the dichloromethane extract of Turmeric, Curcumin and Resveratrol in skin cancer cell was investigated in epidermoid carcinoma cell line A-431. We found that Resveratrol, Turmeric and Curcumin suppressed cell migration and induced cell cycle arrest and apoptosis in cultured A431 skin SCC cells. These effects were associated with modulation of autophagy. Knock-down of the autophagy protein BECLIN 1 partly rescued p53 stability and led to p21-dependent cell cycle arrest. Rapamycin-mediated inhibition of mTOR increased the production of autophagosomes and greatly enhanced Turmeric and Curcumin toxicity. Moreover, A synergistic inhibitory effect on cell migration was observed in the combination Resveratrol plus rapamycin, as mTOR-dependent autophagy inducer or plus LiCl, as mTOR-independent autophagy inducer. The present data support the utilization of Thai herbs extracts in anti-UV cosmetic pharmaceuticals. Moreover, Thai herbs exert important anticancer effects toward skin carcinoma cells by limiting their cell migration and cell proliferation. These effects depend on the modulation of autophagy, a pro-survival pathway.