The current options for treating human cancer are limited to excision surgery, general chemotherapy, radiation therapy and, in a minority of breast cancers that rely on estrogen for their growth, antiestrogen therapy. Although there has been considerable improvement in the treatment of cancer, the overall prognosis remains not good. Therefore, investigators continue to search for new therapeutic strategies. One approach, as pursued in our study, seeks to identify medicinal agents capable of retarding the cell cycle and/or activating the cellular apoptotic response in the cancerous cells.Recently, we have shown that a number of antifungal agents exert antiproliferative and/or apoptotic activities in various malignant cells in vitro and in vivo. For instance, our previous studies showed that ketoconazole (Nizoral) induced cell cycle arrest at the G0/G1 phase of the cell cycle and the occurrence of apoptosis in hepatoma and colon cancer cells, 1,2 whereas griseofulvin (Grifulvin) induced apoptosis and cell cycle arrest at the G2/M phase through abnormal microtubule polymerization. 3 We also showed that combined treatment of griseofulvin and nocodazole (ND) significantly enhanced the therapeutic efficacy in the treatment of cancerous cells in athymic mice bearing COLO 205 tumor xenografts. 3 In the present study, we examined the antitumoral activity of terbinafine (TB) (Lamisil).TB is a newly synthesized oral antimycotic drug in the allylamines class: a fungicidal agent that inhibits ergosterol synthesis at the stage of squalene epoxidation. 4 It shows a good safety profile and relatively few drug interactions. 5 The cream form and oral tablet of TB have been approved for clinical uses in the United States. 6 The oral formulation has been on the market in various countries for more than 8 years, and as of 1997, more than 7.5 million individuals had been treated with this drug. 7 Here, we showed that TB inhibited the proliferation of tumor cells in vitro and in vivo. The experimental findings reported below highlight the molecular mechanisms of TB-induced antitumoral activity.
MATERIAL AND METHODS
Cell lines and cell cultureThe HT 29 (p53 mutant) 8 and COLO 205 (p53 wild) 9 cell lines were isolated from human colon adenocarcinoma (American Type