According to the recently information release from the Department of Health, the malignant tumor is the number 1 cause of death in Taiwan for the last 27 years. Although, several great improvement have been established for treating cancer, developing the drug resistance by the cancer cells causes the curative effect generally not good. Therefore, the new antitumor medicine''s research and development appear urgent. At present the source of antitumor agents is major isolated or derivatives from the plant or the animal, but recently, several studies demonstrated that the fungus also obtain the effective anti-tumor active compounds. In this study, we identified a fungal secondary metabolite, cephalochromin, which posseses a strong antitumoral activity against several human cancer cell lines. Since cephalochromin exerts comparably great anti-proliferative effect toward human nasopharyngeal carcinoma HONE-1 and NPC-TW01 cells, we therefore investigated the mechanisms of action of anticancer efficacy of cephalochromin in this type of cancer. Results demonstrated that cephalochromin induces cells arrest in the G1 phase in the time- and doseage-dependent manner. Significant appearance of sub-G1 population and Annexin V-positive cells indicates that cephalochromin-induced cell death proceeded through an apoptotic pathway. Furthermore, we found that cephalochromin only activate the caspase-8, but not caspase-9. The finding that cephalochromin-induced apoptosis through a memebrane-mediated mechanism was supported by up-regulated expression of Fas and FasL. Furthermore, up-regulation of p53 was found after cephalochromin exposure. Above results indicated that cephalochromin is a effective anticancer agent which could induced cancer cell apoptosis through a p53-mediated caspase-8 / Fas-FasL-dependent pathway and worth for further development.
