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Int. J. Mol. Sci. 2014, 15(3), 4201-4220; doi:10.3390/ijms15034201
Article

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

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Received: 23 January 2014; in revised form: 19 February 2014 / Accepted: 21 February 2014 / Published: 10 March 2014
(This article belongs to the Special Issue Bioactive Lipids and Lipidomics)
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Abstract: 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.
Keywords: ceramide; docetaxel; combination therapy; anti-cancer; synergy mechanisms ceramide; docetaxel; combination therapy; anti-cancer; synergy mechanisms
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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MDPI and ACS Style

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.

AMA Style

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. International Journal of Molecular Sciences. 2014; 15(3):4201-4220.

Chicago/Turabian Style

Feng, Li-Xia; Li, Min; Liu, Yong-Jun; Yang, Shao-Mei; Zhang, Na. 2014. "Synergistic Enhancement of Cancer Therapy Using a Combination of Ceramide and Docetaxel." Int. J. Mol. Sci. 15, no. 3: 4201-4220.



Int. J. Mol. Sci. EISSN 1422-0067 Published by MDPI AG, Basel, Switzerland RSS E-Mail Table of Contents Alert