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Open AccessArticle

Synergistic Enhancement of Cancer Therapy Using a Combination of Ceramide and Docetaxel

Department of Pharmaceutics, College of Pharmacy, Shandong University, 44 West Culture Road, Ji'nan 250012, China
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2014, 15(3), 4201-4220;
Received: 23 January 2014 / Revised: 19 February 2014 / Accepted: 21 February 2014 / Published: 10 March 2014
(This article belongs to the Special Issue Bioactive Lipids and Lipidomics)
Ceramide (CE)-based combination therapy (CE combination) as a novel therapeutic strategy has attracted great attention in the field of anti-cancer therapy. The principal purposes of this study were to investigate the synergistic effect of CE in combination with docetaxel (DTX) (CE + DTX) and to explore the synergy mechanisms of CE + DTX. The 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and combination index (CI) assay showed that simultaneous administration of CE and DTX with a molar ratio of 0.5:1 could generate the optimal synergistic effect on murine malignant melanoma cell (B16, CI = 0.31) and human breast carcinoma cell (MCF-7, CI = 0.48). The apoptosis, cell cycle, and cytoskeleton destruction study demonstrated that CE could target and destruct the microfilament actin, subsequently activate Caspase-3 and induce apoptosis. Meanwhile, DTX could target and disrupt the microtubules cytoskeleton, leading to a high proportion of cancer cells in G2/M-phase arrest. Moreover, CE plus DTX could cause a synergistic destruction of cytoskeleton, which resulted in a significantly higher apoptosis and a significantly higher arrest in G2/M arrest comparing with either agent alone (p < 0.01). The in vivo antitumor study evaluated in B16 tumor-bearing mice also validated the synergistic effects. All these results suggested that CE could enhance the antitumor activity of DTX in a synergistic manner, which suggest promising application prospects of CE + DTX combination treatment. View Full-Text
Keywords: ceramide; docetaxel; combination therapy; anti-cancer; synergy mechanisms ceramide; docetaxel; combination therapy; anti-cancer; synergy mechanisms
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Feng, L.-X.; Li, M.; Liu, Y.-J.; Yang, S.-M.; Zhang, N. Synergistic Enhancement of Cancer Therapy Using a Combination of Ceramide and Docetaxel. Int. J. Mol. Sci. 2014, 15, 4201-4220.

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