Objectives: Determination of the molecular mechanisms of the antiproliferative effect of taxol in human leukemia, breast and ovarian carcinoma cell lines. Methods: Antiproliferative effects of the drug were studied by using clonogenic and growth-inhibition assays. Taxol induced apoptosis was studied by microscopic determination of morphologic signs of programmed cell death and by detecting internucleosomal DNA fragmentation characteristic of apoptosis. To detect alterations of gene expressions mediating apoptosis and inhibition of cell proliferation, Northem-blot analyses were carried out. Results and conclusions: Taxol proved to be a potent antiproliferative agent in all three cell lines. Apoptosis had a major importance in the antiproliferative effect of taxol, however, differentiation was also observed. Induction of apoptosis showed a dose- and time-dependent pattern. Taxol exposure resulted in down-regulation of the c-myc oncogene but had no effect of the transcript levels on other genes studied (p53, bcl-2). Either p53-dependent or -independent pathways could be considered as possible mechanisms for induction of apoptosis by taxol in these cell lines.
|Translated title of the contribution||Molecular mechanisms in the antiproliferative effect of taxol|
|Number of pages||5|
|Publication status||Published - Dec 1 1996|
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