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Bcl-2 down-regulation is a novel mechanism of paclitaxel resistance.
2003 SEP 4 - (NewsRx.com & NewsRx.net) -- Bcl-2 down-regulation is a novel mechanism of paclitaxel resistance.
"Taxanes act by inhibiting microtubule dynamics; in this study, we have investigated mitochondria as an additional target of taxanes. We incubated isolated mitochondria in the presence of taxanes with or without stimulation of the mitochondrial respiratory state," scientists in Italy report.
"Results showed that they rapidly induced the loss of deltapsi(m) after stimulation of the respiratory state. To evaluate the binding of [[superscript]14C] paclitaxel to isolated mitochondria, mitochondrial proteins were precipitated yielding 18.6 [+ or -] 2.1 cpm/microgram of protein," wrote C. Ferlini and colleagues, Sacred Heart University, Department of Obstetrics & Gynecology.
"After stimulation of the respiratory state, binding of [[superscript]14C]paclitaxel increased up to 163.2 [+ or -] 46.7 cpm/microgram of protein. CPM values after Bcl-2 immunoprecipitation was 62.8-fold higher than those of the control antibody, thereby indicating the involvement of Bcl-2 in paclitaxel binding," the researchers wrote.
"Then, we established a panel of A2780 cell lines resistant to increasing doses of paclitaxel alone or to high doses of paclitaxel/cyclosporin A A2780 TC cells). In both cases, Bcl-2 expression was consistently down-regulated, whereas levels of other members of the Bcl-2 family, such as Bax and Bcl-x, did not change in ...
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Source: HighBeam Research, Bcl-2 down-regulation is a novel mechanism of paclitaxel resistance.