Abstract
Inhibitors of topoisomerase I, such as camptothecin, have proven to be among the most promising new classes of anti-neoplastic agents introduced into the clinical setting in recent years. Irinotecan (CPT-11) is one of the most widely used camptothecin analogs and is converted to form the active metabolite SN-38. The present study was designed to explore apoptosis induced by SN38 and anti-Fas antibody (CH11) in WR/Fas-SMS1 cells and its possible mechanisms. The results demonstrate that combination of SN38 and CH11 synergistically enhanced cell apoptosis in WR/Fas-SMS1 cells. Western blotting analysis showed that combination of SN38 and CH11 activated the ATM-Chk1-p53 pathway, increased protein expression of phospho-p53 and cleavaged caspase-3, but down-regulated expression of phospho-p21. Our data suggest that combination of SN38 and CH11 enhanced apoptosis through down-regulation of p21 phosphorylation. In conclusion, inhibition of p21 could be a new adjuvant approach in cancer therapy.
- Received May 31, 2010.
- Revision received July 27, 2010.
- Accepted August 10, 2010.
- Copyright© 2010 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved