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Molecular and Clinical Oncology
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November-December 2014 Volume 2 Issue 6

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International Journal of Molecular Medicine

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

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

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

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

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

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

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

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Article

Ritonavir acts synergistically with panobinostat to enhance histone acetylation and inhibit renal cancer growth

  • Authors:
    • Akinori Sato
    • Takako Asano
    • Makoto Isono
    • Keiichi Ito
    • Tomohiko Asano
  • View Affiliations / Copyright

    Affiliations: Department of Urology, National Defense Medical College, Tokorozawa, Saitama 359‑8513, Japan
  • Pages: 1016-1022
    |
    Published online on: July 15, 2014
       https://doi.org/10.3892/mco.2014.349
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Abstract

There is currently no curative treatment for advanced renal cancer. Enhancing histone acetylation is a promising epigenetic‑based therapy for cancer; however, in solid tumors, the efficacy of histone deacetylase (HDAC) inhibitors alone is limited. The human immunodeficiency virus protease inhibitor ritonavir is also a CYP3A4 inhibitor and we hypothesized that combining ritonavir with the HDAC inhibitor panobinostat, one of the substrates of CYP3A4, may effectively eliminate renal cancer cells by enhancing the activity of panobinostat. The combination of ritonavir and panobinostat synergistically inhibited cancer cell growth and cancer cell colony formation, while only slightly inhibiting the growth of renal proximal tubule epithelial cells. This combination significantly induced apoptosis in cancer cells and this apoptosis was considered to be caspase‑dependent, since the pan‑caspase inhibitor Z‑VAD‑FMK reduced the number of Annexin V‑positive cells. In murine subcutaneous xenograft models using Caki‑1 cells, a 10‑day treatment with the combination of ritonavir and panobinostat significantly inhibited tumor growth. Panobinostat alone increased histone acetylation in a dose‑dependent manner and the co-administration of ritonavir synergistically enhanced this acetylation. Furthermore, this combination inhibited the expression of HDACs, which may also play a role in the enhancement of histone acetylation. Thus, the present study may provide a basis for testing the combination of ritonavir and panobinostat for patients with advanced renal cancer.
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Copy and paste a formatted citation
Spandidos Publications style
Sato A, Asano T, Isono M, Ito K and Asano T: Ritonavir acts synergistically with panobinostat to enhance histone acetylation and inhibit renal cancer growth. Mol Clin Oncol 2: 1016-1022, 2014.
APA
Sato, A., Asano, T., Isono, M., Ito, K., & Asano, T. (2014). Ritonavir acts synergistically with panobinostat to enhance histone acetylation and inhibit renal cancer growth. Molecular and Clinical Oncology, 2, 1016-1022. https://doi.org/10.3892/mco.2014.349
MLA
Sato, A., Asano, T., Isono, M., Ito, K., Asano, T."Ritonavir acts synergistically with panobinostat to enhance histone acetylation and inhibit renal cancer growth". Molecular and Clinical Oncology 2.6 (2014): 1016-1022.
Chicago
Sato, A., Asano, T., Isono, M., Ito, K., Asano, T."Ritonavir acts synergistically with panobinostat to enhance histone acetylation and inhibit renal cancer growth". Molecular and Clinical Oncology 2, no. 6 (2014): 1016-1022. https://doi.org/10.3892/mco.2014.349
Copy and paste a formatted citation
x
Spandidos Publications style
Sato A, Asano T, Isono M, Ito K and Asano T: Ritonavir acts synergistically with panobinostat to enhance histone acetylation and inhibit renal cancer growth. Mol Clin Oncol 2: 1016-1022, 2014.
APA
Sato, A., Asano, T., Isono, M., Ito, K., & Asano, T. (2014). Ritonavir acts synergistically with panobinostat to enhance histone acetylation and inhibit renal cancer growth. Molecular and Clinical Oncology, 2, 1016-1022. https://doi.org/10.3892/mco.2014.349
MLA
Sato, A., Asano, T., Isono, M., Ito, K., Asano, T."Ritonavir acts synergistically with panobinostat to enhance histone acetylation and inhibit renal cancer growth". Molecular and Clinical Oncology 2.6 (2014): 1016-1022.
Chicago
Sato, A., Asano, T., Isono, M., Ito, K., Asano, T."Ritonavir acts synergistically with panobinostat to enhance histone acetylation and inhibit renal cancer growth". Molecular and Clinical Oncology 2, no. 6 (2014): 1016-1022. https://doi.org/10.3892/mco.2014.349
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