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The Possible Correlation Between Activation of NF-κB/IκB Pathway and the Susceptibility of Tumor Cells to Paclitaxel-Induced Apoptosis

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Abstract:

Paclitaxel (Taxol®) is a naturally occurring antimitotic agent that has been shown to induce apoptosis in both leukemic and solid tumor cells, but many tumor cells exhibit a high resistance to paclitaxel. The mechanism of different susceptibility among tumor cells to paclitaxel-induced apoptotic cell death is not entirely clear. In this study, we identified and characterized two solid tumor cell lines, human breast tumor MCF7 cells and rat prostate tumor R3227 cells, which were resistant to paclitaxel-induced apoptosis. The results indicated that these tumor cells were highly resistant to paclitaxel-induced nucleosomal DNA fragmentation, but still sensitive to paclitaxel-induced microtubule bundling and cell cycle arrest at G2-M. This selective resistance of MCF7 and R3227 to paclitaxel suggests that mitotic arrest and apoptotic cell death might be two separate events, and paclitaxel-induced mitotic arrest may not always be followed by apoptotic cell death. Further, through comparative studies and analyses of a number of genes whose expression or activation may be involved in the regulation of apoptotic cell death or drug resistance, we found that paclitaxel induced the degradation of IκBα protein, which in turn activated NF-κB in paclitaxel-sensitive tumor cells, but such a paclitaxel-induced activation of the NF-κB/IκBα cascade was not observed in either MCF7 or R3227 cells. These findings suggest that the activation of NF-κB/IκBα signaling pathway might play an important role in determining the susceptibility of tumor cells to paclitaxel-induced apoptosis.

Keywords: Apoptosis; Key words: Paclitaxel; Mitotic arrest; NF-κB/IκB

Document Type: Research Article

DOI: https://doi.org/10.3727/096504002108748150

Affiliations: 1: *Department of Pathology and Laboratory Medicine, Medical University of South Carolina, 171 Ashley Avenue, Charleston, SC 29425 2: †Department of Microbiology and Immunology, Medical University of South Carolina, 171 Ashley Avenue, Charleston, SC 29425

Publication date: 2002-02-01

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  • Formerly: Oncology Research Incorporating Anti-Cancer Drug Design
    Oncology Research Featuring Preclinical and Clincal Cancer Therapeutics publishes research of the highest quality that contributes to an understanding of cancer in areas of molecular biology, cell biology, biochemistry, biophysics, genetics, biology, endocrinology, and immunology, as well as studies on the mechanism of action of carcinogens and therapeutic agents, reports dealing with cancer prevention and epidemiology, and clinical trials delineating effective new therapeutic regimens.
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