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International Journal of Oncology
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Print ISSN: 1019-6439 Online ISSN: 1791-2423
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March 2011 Volume 38 Issue 3

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Journals

International Journal of Molecular Medicine

International Journal of Molecular Medicine

International Journal of Molecular Medicine is an international journal devoted to molecular mechanisms of human disease.

International Journal of Oncology

International Journal of Oncology

International Journal of Oncology is an international journal devoted to oncology research and cancer treatment.

Molecular Medicine Reports

Molecular Medicine Reports

Covers molecular medicine topics such as pharmacology, pathology, genetics, neuroscience, infectious diseases, molecular cardiology, and molecular surgery.

Oncology Reports

Oncology Reports

Oncology Reports is an international journal devoted to fundamental and applied research in Oncology.

Experimental and Therapeutic Medicine

Experimental and Therapeutic Medicine

Experimental and Therapeutic Medicine is an international journal devoted to laboratory and clinical medicine.

Oncology Letters

Oncology Letters

Oncology Letters is an international journal devoted to Experimental and Clinical Oncology.

Biomedical Reports

Biomedical Reports

Explores a wide range of biological and medical fields, including pharmacology, genetics, microbiology, neuroscience, and molecular cardiology.

Molecular and Clinical Oncology

Molecular and Clinical Oncology

International journal addressing all aspects of oncology research, from tumorigenesis and oncogenes to chemotherapy and metastasis.

World Academy of Sciences Journal

World Academy of Sciences Journal

Multidisciplinary open-access journal spanning biochemistry, genetics, neuroscience, environmental health, and synthetic biology.

International Journal of Functional Nutrition

International Journal of Functional Nutrition

Open-access journal combining biochemistry, pharmacology, immunology, and genetics to advance health through functional nutrition.

International Journal of Epigenetics

International Journal of Epigenetics

Publishes open-access research on using epigenetics to advance understanding and treatment of human disease.

Medicine International

Medicine International

An International Open Access Journal Devoted to General Medicine.

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March 2011 Volume 38 Issue 3

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Article

The chemosensitizing activity of inhibitors of glucosylceramide synthase is mediated primarily through modulation of P-gp function

  • Authors:
    • Lilly Chai
    • Rajashree P. McLaren
    • Ann Byrne
    • Wei-Lien Chuang
    • Yinyin Huang
    • Michael R. Dufault
    • Joshua Pacheco
    • Shruti Madhiwalla
    • Xiaokui Zhang
    • Mindy Zhang
    • Beverly A. Teicher
    • Kara Carter
    • Seng H. Cheng
    • John P. Leonard
    • Yibin Xiang
    • Michael Vasconcelles
    • Mark A. Goldberg
    • Diane P. Copeland
    • Katherine W. Klinger
    • James Lillie
    • Stephen L. Madden
    • Yide A. Jiang
  • View Affiliations / Copyright

    Affiliations: Genzyme Corporation, 49 New York Avenue, Framingham, MA 01701, USA
  • Pages: 701-711
    |
    Published online on: December 24, 2010
       https://doi.org/10.3892/ijo.2010.888
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Abstract

Glucosylceramide synthase (GCS) is a key enzyme engaged in the biosynthesis of glycosphingolipids and in regulating ceramide metabolism. Studies exploring alterations in GCS activity suggest that the glycolase may have a role in chemosensitizing tumor cells to various cancer drugs. The chemosensitizing effect of inhibitors of GCS (e.g. PDMP and selected analogues) has been observed with a variety of tumor cells leading to the proposal that the sensitizing activity of GCS inhibitors is primarily through increases in intracellular ceramide leading to induction of apoptosis. The current study examined the chemosensitizing activity of the novel GCS inhibitor, Genz-123346 in cell culture. Exposure of cells to Genz-123346 and to other GCS inhibitors at non-toxic concentrations can enhance the killing of tumor cells by cytotoxic anti-cancer agents. This activity was unrelated to lowering intracellular glycosphingolipid levels. Genz-123346 and a few other GCS inhibitors are substrates for multi-drug reisistance efflux pumps such as P-gp (ABCB1, gP-170). In cell lines selected to over-express P-gp or which endogenously express P-gp, chemosensitization by Genz-123346 was primarily due to the effects on P-gp function. RNA interference studies using siRNA or shRNA confirmed that lowering GCS expression in tumor cells did not affect their responsiveness to commonly used cytotoxic drugs.

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Copy and paste a formatted citation
Spandidos Publications style
Chai L, McLaren RP, Byrne A, Chuang W, Huang Y, Dufault MR, Pacheco J, Madhiwalla S, Zhang X, Zhang M, Zhang M, et al: The chemosensitizing activity of inhibitors of glucosylceramide synthase is mediated primarily through modulation of P-gp function. Int J Oncol 38: 701-711, 2011.
APA
Chai, L., McLaren, R.P., Byrne, A., Chuang, W., Huang, Y., Dufault, M.R. ... Jiang, Y.A. (2011). The chemosensitizing activity of inhibitors of glucosylceramide synthase is mediated primarily through modulation of P-gp function. International Journal of Oncology, 38, 701-711. https://doi.org/10.3892/ijo.2010.888
MLA
Chai, L., McLaren, R. P., Byrne, A., Chuang, W., Huang, Y., Dufault, M. R., Pacheco, J., Madhiwalla, S., Zhang, X., Zhang, M., Teicher, B. A., Carter, K., Cheng, S. H., Leonard, J. P., Xiang, Y., Vasconcelles, M., Goldberg, M. A., Copeland, D. P., Klinger, K. W., Lillie, J., Madden, S. L., Jiang, Y. A."The chemosensitizing activity of inhibitors of glucosylceramide synthase is mediated primarily through modulation of P-gp function". International Journal of Oncology 38.3 (2011): 701-711.
Chicago
Chai, L., McLaren, R. P., Byrne, A., Chuang, W., Huang, Y., Dufault, M. R., Pacheco, J., Madhiwalla, S., Zhang, X., Zhang, M., Teicher, B. A., Carter, K., Cheng, S. H., Leonard, J. P., Xiang, Y., Vasconcelles, M., Goldberg, M. A., Copeland, D. P., Klinger, K. W., Lillie, J., Madden, S. L., Jiang, Y. A."The chemosensitizing activity of inhibitors of glucosylceramide synthase is mediated primarily through modulation of P-gp function". International Journal of Oncology 38, no. 3 (2011): 701-711. https://doi.org/10.3892/ijo.2010.888
Copy and paste a formatted citation
x
Spandidos Publications style
Chai L, McLaren RP, Byrne A, Chuang W, Huang Y, Dufault MR, Pacheco J, Madhiwalla S, Zhang X, Zhang M, Zhang M, et al: The chemosensitizing activity of inhibitors of glucosylceramide synthase is mediated primarily through modulation of P-gp function. Int J Oncol 38: 701-711, 2011.
APA
Chai, L., McLaren, R.P., Byrne, A., Chuang, W., Huang, Y., Dufault, M.R. ... Jiang, Y.A. (2011). The chemosensitizing activity of inhibitors of glucosylceramide synthase is mediated primarily through modulation of P-gp function. International Journal of Oncology, 38, 701-711. https://doi.org/10.3892/ijo.2010.888
MLA
Chai, L., McLaren, R. P., Byrne, A., Chuang, W., Huang, Y., Dufault, M. R., Pacheco, J., Madhiwalla, S., Zhang, X., Zhang, M., Teicher, B. A., Carter, K., Cheng, S. H., Leonard, J. P., Xiang, Y., Vasconcelles, M., Goldberg, M. A., Copeland, D. P., Klinger, K. W., Lillie, J., Madden, S. L., Jiang, Y. A."The chemosensitizing activity of inhibitors of glucosylceramide synthase is mediated primarily through modulation of P-gp function". International Journal of Oncology 38.3 (2011): 701-711.
Chicago
Chai, L., McLaren, R. P., Byrne, A., Chuang, W., Huang, Y., Dufault, M. R., Pacheco, J., Madhiwalla, S., Zhang, X., Zhang, M., Teicher, B. A., Carter, K., Cheng, S. H., Leonard, J. P., Xiang, Y., Vasconcelles, M., Goldberg, M. A., Copeland, D. P., Klinger, K. W., Lillie, J., Madden, S. L., Jiang, Y. A."The chemosensitizing activity of inhibitors of glucosylceramide synthase is mediated primarily through modulation of P-gp function". International Journal of Oncology 38, no. 3 (2011): 701-711. https://doi.org/10.3892/ijo.2010.888
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