Differential Activity of Caspase-3 Regulates Susceptibility of Lung and Breast Tumor Cell Lines to Paclitaxel



Charles Amoatey Odonkor, Samuel Achilefu*


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© Odonkor and Achilefu; Licensee Bentham Open

open-access license: This is an open access article licensed under the terms of the Creative Commons Attribution Non-Commercial License (http: //creativecommons.org/licenses/by-nc/3.0/) which permits unrestricted, non-commercial use, distribution and reproduction in any medium, provided the work is properly cited.

* Address correspondence to this author at the Department of Radiology, Washington University School of Medicine, 4525 Scott Avenue, St. Louis, MO 63110, USA; Tel: +1-314-362-8599; Fax: +1-314-747-5191; Email: achilefus@mir.wustl.edu


Abstract

Recent development of tumor resistance to paclitaxel presents a major problem to cancer treatment. An unsettled controversy in the cancer chemotherapy field, however, is whether caspases play a prominent role in paclitaxel-induced death in tumors. Previous studies suggest that cleavage of caspase-3 is not instrumental for the execution of death in tumors treated with paclitaxel, while other reports indicate that caspase-dependent pathways may be critical for paclitaxel cytotoxicity. In this study, we investigated the role of caspase-3 in breast and lung tumor cell line sensitivity to paclitaxel. Clonogenic survival and live/dead viability-assays, together with enzymatic activity and cell proliferation assays, reveal that the levels of paclitaxel-induced caspase-3 enzymatic activity in tumor cells correlate directly with tumor sensitivity to the drug.We observed a 2-fold increase in caspase-3 activity in 4T1-Luc breast tumor cells, but a 3-fold and 4-fold decrease in A549 and A427 lung tumor cell lines, respectively. Together, our results suggest that caspase-activation and activity levels are not only key determinants of paclitaxel-induced death in tumors but also serve as good indicators for tumor susceptibility to paclitaxel therapy. Our studies also indicate that within clinically relevant doses of paclitaxel, the ability to rid tumor populations of dormant tumor cells controls the rate of tumor recurrence.

Keywords: Casapse-3, breast tumor, paclitaxel, apoptosis.