Abstract
The objective of this study was to determine the effect of Cremophor (CrEL) on the antineoplastic effect induced by paclitaxel (PTX). Fluorescence spectroscopy, employing pyrene as a probe, was used to determine the critical micelle concentration (CMC) of CrEL. EL4 murine thymoma cells and MDA-MB-231 human breast cancer cells were treated with PTX in different concentrations of CrEL.G2 arrest with 8 N polyploidy was observed in PTX-treated EL4 cells but not in MDA-MB-231 cells. Cell cycle analysis via propidium iodide (PI) staining showed that the frequency of G2 arrest decreased as the CrEL concentration exceeded 0.02% (w/v), demonstrating the effect of CrEL micelle formation on the antimitotic activity of PTX. CrEL was also shown to enhance PTX-induced cell death in vitro by Annexin V/PI staining. Treatment of C57BL/6 mice with PTX in a lower concentration of CrEL resulted in higher myelosuppression, decreased both Ki-67 expression and survival rate, suggesting that CrEL micelle formation above the CMC may lower the cytotoxic activity of PTX in vivo.The data obtained in this study demonstrate CrEL micelle-mediated modulation of the cell cycle and cell death induced by PTX in vitro and the antineoplastic efficacy of PTX in vivo.
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