Skip to main content
Journal cover image

Mechanism of anti-glioma activity and in vivo efficacy of the cannabinoid ligand KM-233.

Publication ,  Journal Article
Gurley, SN; Abidi, AH; Allison, P; Guan, P; Duntsch, C; Robertson, JH; Kosanke, SD; Keir, ST; Bigner, DD; Elberger, AJ; Moore, BM
Published in: J Neurooncol
November 2012

Glioblastoma multiforme (GBM) is the most common and devastating form of primary central nervous system malignancy. The prognosis for patients diagnosed with GBM is poor, having a median survival rate of 12-15 months. Despite modern advances in the development of antineoplastic agents, the efficacy of newer anti-cancer agents in the treatment of GBM is yet to be determined. Thus, there remains a significant unmet need for new therapeutic strategies against GBM. A promising chemotherapeutic intervention has emerged from studies of cannabinoid receptor agonists wherein tetrahydrocannabinol has been the most extensively studied. The novel cannabinoid ligand KM-233 was developed as a lead platform for future optimization of biopharmaceutical properties of classical based cannabinoid ligands. Treatment of U87MG human GBM cells with KM-233 caused a time dependent change in the phosphorylation profiles of MEK, ERK1/2, Akt, BAD, STAT3, and p70S6K. Almost complete mitochondrial depolarization was observed 6 h post-treatment followed by a rapid increase in cleaved caspase 3 and significant cytoskeletal contractions. Treatment with KM-233 also resulted in a redistribution of the Golgi-endoplasmic reticulum structures. Dose escalation studies in the orthotopic model using U87MG cells revealed an 80 % reduction in tumor size after 12 mg/kg daily dosing for 20 days. The evaluation of KM-233 against primary tumor tissue in the side flank model revealed a significant decrease in the rate of tumor growth. These findings indicate that structural refinement of KM-233 to improve its biopharmaceutical properties may lead to a novel and efficacious treatment for GBM.

Duke Scholars

Altmetric Attention Stats
Dimensions Citation Stats

Published In

J Neurooncol

DOI

EISSN

1573-7373

Publication Date

November 2012

Volume

110

Issue

2

Start / End Page

163 / 177

Location

United States

Related Subject Headings

  • Tumor Cells, Cultured
  • Receptor, Cannabinoid, CB2
  • Receptor, Cannabinoid, CB1
  • Phosphoproteins
  • Oncology & Carcinogenesis
  • Mice, SCID
  • Mice, Inbred BALB C
  • Mice
  • Membrane Potential, Mitochondrial
  • Male
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Gurley, S. N., Abidi, A. H., Allison, P., Guan, P., Duntsch, C., Robertson, J. H., … Moore, B. M. (2012). Mechanism of anti-glioma activity and in vivo efficacy of the cannabinoid ligand KM-233. J Neurooncol, 110(2), 163–177. https://doi.org/10.1007/s11060-012-0958-5
Gurley, Steven N., Ammaar H. Abidi, Patrick Allison, Peihong Guan, Christopher Duntsch, Jon H. Robertson, Stanley D. Kosanke, et al. “Mechanism of anti-glioma activity and in vivo efficacy of the cannabinoid ligand KM-233.J Neurooncol 110, no. 2 (November 2012): 163–77. https://doi.org/10.1007/s11060-012-0958-5.
Gurley SN, Abidi AH, Allison P, Guan P, Duntsch C, Robertson JH, et al. Mechanism of anti-glioma activity and in vivo efficacy of the cannabinoid ligand KM-233. J Neurooncol. 2012 Nov;110(2):163–77.
Gurley, Steven N., et al. “Mechanism of anti-glioma activity and in vivo efficacy of the cannabinoid ligand KM-233.J Neurooncol, vol. 110, no. 2, Nov. 2012, pp. 163–77. Pubmed, doi:10.1007/s11060-012-0958-5.
Gurley SN, Abidi AH, Allison P, Guan P, Duntsch C, Robertson JH, Kosanke SD, Keir ST, Bigner DD, Elberger AJ, Moore BM. Mechanism of anti-glioma activity and in vivo efficacy of the cannabinoid ligand KM-233. J Neurooncol. 2012 Nov;110(2):163–177.
Journal cover image

Published In

J Neurooncol

DOI

EISSN

1573-7373

Publication Date

November 2012

Volume

110

Issue

2

Start / End Page

163 / 177

Location

United States

Related Subject Headings

  • Tumor Cells, Cultured
  • Receptor, Cannabinoid, CB2
  • Receptor, Cannabinoid, CB1
  • Phosphoproteins
  • Oncology & Carcinogenesis
  • Mice, SCID
  • Mice, Inbred BALB C
  • Mice
  • Membrane Potential, Mitochondrial
  • Male