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Proteasome inhibitor Carfilzomib enhances the anti cancer effect of Paclitaxel in MDA-MB-231 breast cancer cells

By: Terzi, Hatice.
Contributor(s): Mustafa, E | Mehmet, S | Ahmet, A | Ergul, Merve.
Publisher: Mumbai Indian Journal of Pharmaceutical Science 2019Edition: Vol.81(6), November-December.Description: 1146-1153p.Subject(s): PHARMACEUTICSOnline resources: Click here In: Indian journal of pharmaceutical sciencesSummary: This study was aimed to determine the anticancer efficacy of the combination of paclitaxel, the standard treatment of breast cancer, and carfilzomib, which is a proteasome inhibitor, in breast cancer cells in vitro. Paclitaxel, Carfilzomib and their combinations at various concentrations were added to MDA-MB-231 human breast cancer cells, and cell viability was detected using the XTT assay. Combination index values were determined using the Chou-Talalay method. Apoptotic effect and cell cycle arrest of single administrations and combinations of these agents were also evaluated using the ow cytometry. According to the results of the XTT assay, the combination produced a greater anticancer effect than that produced by both agents administered alone. Chou-Talalay approaches exhibited that the combination of paclitaxel and carlzomib demonstrated a synergistic effect. The ow analysis showed that the combinations have induced a cell cycle arrest of MDA-MB-231 cells at G2/M phase and significantly induced apoptosis. The present study revealed that carfilzomib could significantly increase the efficacy of paclitaxel in human breast cancer cells in vitro. It is recommended that carlzomib to be used along with paclitaxel in metastaticbreast cancer patients to increase the anticancer effect and reduce potential toxicity-related side effects.
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This study was aimed to determine the anticancer efficacy of the combination of paclitaxel, the standard treatment of breast cancer, and carfilzomib, which is a proteasome inhibitor, in breast cancer cells in vitro. Paclitaxel, Carfilzomib and their combinations at various concentrations were added to MDA-MB-231 human breast cancer cells, and cell viability was detected using the XTT assay. Combination index values were determined using the Chou-Talalay method. Apoptotic effect and cell cycle arrest of single administrations and combinations of these agents were also evaluated using the ow cytometry. According to the results of the XTT assay, the combination produced a greater anticancer effect than that produced by both agents administered alone. Chou-Talalay approaches exhibited that the combination of paclitaxel and carlzomib demonstrated a synergistic effect. The ow analysis showed that the combinations have induced a cell cycle arrest of MDA-MB-231 cells at G2/M phase and significantly induced apoptosis. The present study revealed that carfilzomib could significantly increase the efficacy of paclitaxel in human breast cancer cells in vitro. It is recommended that carlzomib to be used along with paclitaxel in metastaticbreast cancer patients to increase the anticancer effect and reduce potential toxicity-related side effects.

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