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Journal of Neuro-Oncology

, Volume 77, Issue 2, pp 143–152 | Cite as

Safety and efficacy of a novel cannabinoid chemotherapeutic, KM-233, for the treatment of high-grade glioma

  • Christopher DuntschEmail author
  • Murali Krishna Divi
  • Terreia Jones
  • Qihong Zhou
  • Mathangi Krishnamurthy
  • Peter Boehm
  • George Wood
  • Allen Sills
  • Bob M. Moore II
Laboratory Investigation

Summary

Objective

To test in vitro and in vivo the safety and efficacy of a novel chemotherapeutic agent, KM-233, for the treatment of glioma.

Methods

In vitro cell cytotoxicity assays were used to measure and compare the cytotoxic effects of KM-233, Δ8-tetrahydrocannabinol (THC), and bis-chloroethyl-nitrosurea (BCNU) against human U87 glioma cells. An organotypic brain slice culture model was used for safety and toxicity studies. A human glioma-SCID mouse side-pocket tumor model was used to test in vivo the safety and efficacy of KM-233 with intratumoral and intra-peritoneal administration.

Results

KM-233 is a classical cannabinoid with good blood brain barrier penetration that possesses a selective affinity for the CB2 receptors relative to THC. KM-233 was as efficacious in its cytotoxicity against human U87 glioma as Δ8-tetrahydrocannabinol, and superior to the commonly used anti-glioma chemotherapeutic agent, BCNU. The cytotoxic effects of KM-233 against human glioma cells in vitro occur as early as two hours after administration, and dosing of KM-233 can be cycled without compromising cytotoxic efficacy and while improving safety. Cyclical dosing of KM-233 to treat U87 glioma in a SCID mouse xenograft side pocket model was effective at reducing the tumor burden with both systemic and intratumoral administration.

Conclusion

These studies provide both in vitro and in vivo evidence that KM-233 shows promising efficacy against human glioma cell lines in both in vitro and in vivo studies, minimal toxicity to healthy cultured brain tissue, and should be considered for definitive preclinical development in animal models of glioma.

Keywords

brain tumor cannabinoid chemotherapeutic glioma therapy 

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Notes

Acknowledgements

This work was supported by a research grant from the Methodist Foundation (Memphis, TN). The authors thank Mariya Nazarova and Dr. Xiaofei Wang for their excellent technical contribution to this work.

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Copyright information

© Springer Science + Business Media Inc., 2005

Authors and Affiliations

  • Christopher Duntsch
    • 1
    • 4
    Email author
  • Murali Krishna Divi
    • 2
  • Terreia Jones
    • 3
  • Qihong Zhou
    • 1
  • Mathangi Krishnamurthy
    • 2
  • Peter Boehm
    • 1
  • George Wood
    • 2
  • Allen Sills
    • 1
  • Bob M. Moore II
    • 2
  1. 1.Departments of NeurosurgeryThe University of Tennessee Health Science CenterMemphisUSA
  2. 2.Department of Pharmaceutical SciencesThe University of Tennessee Health Science CenterMemphisUSA
  3. 3.Department of PharmacyThe University of Tennessee Health Science CenterMemphisUSA
  4. 4.Departments of NeurosurgeryThe University of Tennessee Health Science CenterMemphisUSA

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