Ugonin K induces Cell Cycle Arrest and Apoptosis through Reactive oxygen species/Apoptosis Signal Pathway in Human Skin Cancer Cells

摘要

The incidence and mortality of skin cancer continue to rise because of the destruction of the ozonosphere in the earth. Skin cancer is divided into two groups by histological features - nonmelanoma skin cancers (NMSC) and melanoma. Cutaneous basal cell carcinoma (BCC) and squamous cell carcinoma (SCC) of NMSC are almost 75% among human skin malignancy cancer. In the preliminary bioactivity screening, the compound isolated from Helminthostachys zeylanica were evaluated antioxidant activities and interacted individually with serial human cancer cells, results that antioxidant activities of ugonin K were evaluated by measuring DPPH free-radical scavenging activities, and reducing power. Determination the reactive oxygen species (ROS) content and reduced glutathione (GSH) formation in H_2O_2-treated HaCaT cells by ugonin K. The cytotoxicity results show that ugonin K expressed less toxic to human keratinocytes (HaCaT cells) and human skin fibroblasts (Hs68 cells) than BCC cells, suggesting that ugonin K may have potential to be developed effective drugs for skin cancer cells without damaging skin normal cells. After treatment with ugonin K in BCC cells, cell cycle arrested in S-G_2/M phase with a markedly increased apoptotic sub-G_1 peak, mitochondria membrane potential (MMP) reduced, the expression of p53, Caspase-8, Caspase-9 and Caspase-3 revealed a more significant increased than the untreated control. Expected ugonin K has potential for an effective and specific drug to cancer cell, can minimize the damage to normal cell and provide a better therapeutic method to skin carcinoma.