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Research ArticleChemotherapy, Antibiotics, and Gene Therapy

Quantitative Analyses of Synergistic Responses between Cannabidiol and DNA-Damaging Agents on the Proliferation and Viability of Glioblastoma and Neural Progenitor Cells in Culture

Liting Deng, Lindsay Ng, Tatsuya Ozawa and Nephi Stella
Journal of Pharmacology and Experimental Therapeutics January 2017, 360 (1) 215-224; DOI: https://doi.org/10.1124/jpet.116.236968
Liting Deng
Departments of Pharmacology, Department of Psychiatry and Behavioral Sciences, University of Washington School of Medicine, Seattle, Washington (L.D., L.N., N.S.); Department of Neurosurgery, Alvord Brain Tumor Center, University of Washington, Seattle, Washington (T.O.); and Division of Human Biology and Solid Tumor Translational Research, Fred Hutchinson Cancer Research Center, Seattle, Washington (T.O.)
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Lindsay Ng
Departments of Pharmacology, Department of Psychiatry and Behavioral Sciences, University of Washington School of Medicine, Seattle, Washington (L.D., L.N., N.S.); Department of Neurosurgery, Alvord Brain Tumor Center, University of Washington, Seattle, Washington (T.O.); and Division of Human Biology and Solid Tumor Translational Research, Fred Hutchinson Cancer Research Center, Seattle, Washington (T.O.)
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Tatsuya Ozawa
Departments of Pharmacology, Department of Psychiatry and Behavioral Sciences, University of Washington School of Medicine, Seattle, Washington (L.D., L.N., N.S.); Department of Neurosurgery, Alvord Brain Tumor Center, University of Washington, Seattle, Washington (T.O.); and Division of Human Biology and Solid Tumor Translational Research, Fred Hutchinson Cancer Research Center, Seattle, Washington (T.O.)
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Nephi Stella
Departments of Pharmacology, Department of Psychiatry and Behavioral Sciences, University of Washington School of Medicine, Seattle, Washington (L.D., L.N., N.S.); Department of Neurosurgery, Alvord Brain Tumor Center, University of Washington, Seattle, Washington (T.O.); and Division of Human Biology and Solid Tumor Translational Research, Fred Hutchinson Cancer Research Center, Seattle, Washington (T.O.)
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Abstract

Evidence suggests that the nonpsychotropic cannabis-derived compound, cannabidiol (CBD), has antineoplastic activity in multiple types of cancers, including glioblastoma multiforme (GBM). DNA-damaging agents remain the main standard of care treatment available for patients diagnosed with GBM. Here we studied the antiproliferative and cell-killing activity of CBD alone and in combination with DNA-damaging agents (temozolomide, carmustine, or cisplatin) in several human GBM cell lines and in mouse primary GBM cells in cultures. This activity was also studied in mouse neural progenitor cells (NPCs) in culture to assess for potential central nervous system toxicity. We found that CBD induced a dose-dependent reduction of both proliferation and viability of all cells with similar potencies, suggesting no preferential activity for cancer cells. Hill plot analysis indicates an allosteric mechanism of action triggered by CBD in all cells. Cotreatment regimens combining CBD and DNA-damaging agents produced synergistic antiproliferating and cell-killing responses over a limited range of concentrations in all human GBM cell lines and mouse GBM cells as well as in mouse NPCs. Remarkably, antagonistic responses occurred at low concentrations in select human GBM cell lines and in mouse GBM cells. Our study suggests limited synergistic activity when combining CBD and DNA-damaging agents in treating GBM cells, along with little to no therapeutic window when considering NPCs.

Footnotes

    • Received August 3, 2016.
    • Accepted November 2, 2016.
  • ↵1 Current affiliation: Division of Brain Tumor Translational Research, National Cancer Center Research Institute, Tokyo, Japan.

  • This research was supported by the National Institutes of Health National Institute on Drug Abuse [Grant R01 DA026430].

  • dx.doi.org/10.1124/jpet.116.236968.

  • ↵Embedded ImageThis article has supplemental material available at jpet.aspetjournals.org.

  • Copyright © 2016 by The American Society for Pharmacology and Experimental Therapeutics
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Journal of Pharmacology and Experimental Therapeutics: 360 (1)
Journal of Pharmacology and Experimental Therapeutics
Vol. 360, Issue 1
1 Jan 2017
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Research ArticleChemotherapy, Antibiotics, and Gene Therapy

Cannabidiol and DNA-Damaging Agents on Glioblastoma

Liting Deng, Lindsay Ng, Tatsuya Ozawa and Nephi Stella
Journal of Pharmacology and Experimental Therapeutics January 1, 2017, 360 (1) 215-224; DOI: https://doi.org/10.1124/jpet.116.236968

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Research ArticleChemotherapy, Antibiotics, and Gene Therapy

Cannabidiol and DNA-Damaging Agents on Glioblastoma

Liting Deng, Lindsay Ng, Tatsuya Ozawa and Nephi Stella
Journal of Pharmacology and Experimental Therapeutics January 1, 2017, 360 (1) 215-224; DOI: https://doi.org/10.1124/jpet.116.236968
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