Analysis of cell cycle gene expression responding to acetoxyscirpendiol isolated from Paecilomyces tenuipes

Abstract

Paecilomyces tenuipes is believed to contain potential oncostatic and tumor-reducing components. Molecular mechanism, however, is poorly understood concerning the potential antitumor components and their biological function. We purified acetoxyscirpendiol (ASD) from methanolic extracts (MPT) of the fungus and tested the two compounds for the molecular profile of their antitumor potential. Using a differential display protocol, cyclin C and Mad-1 were identified as candidate genes responding to MPT. When a quantitative PCR was performed on the total RNA from MCF-7 treated by MPT or ASD, gene expressions of cyclin C and Mad-1 were greatly augmented. In terms of protein expression, cyclin C level increased up to 12 folds in response to ASD as well as MPT. Similar as MPT treatments, ASD-treated cells synthesize cyclin C as 2-4 fold compared to the control treatments. In terms of Mad-1 expression in cells treated with ASD, the level of Mad-1 expression increased up to 2.5 folds by MPT treatment. Cyclin C expression was compared with non-treated cells in various cell lines. MCF-7 cell was shown highly responsive to the MPT or ASD treatment. Taken together, these results strongly indicate that MPT contains potential antitumor components which might exert their action by modulating cell cycle-related genes such as cyclin C and Mad-1 in MCF-7. The major antioncogcnic component in MPT may be ASD which modulates cyclin C and Mad-1 expression.