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Journal of Neuro-Oncology

, Volume 74, Issue 1, pp 31–40 | Cite as

Cannabinoids selectively inhibit proliferation and induce death of cultured human glioblastoma multiforme cells

  • Sean D. Mc Allister
  • Calvin Chan
  • Ryan J. Taft
  • Tri Luu
  • Mary E. Abood
  • Dan H. Moore
  • Ken Aldape
  • Garret Yount
Laboratory Investigation

Summary

Normal tissue toxicity limits the efficacy of current treatment modalities for glioblastoma multiforme (GBM). We evaluated the influence of cannabinoids on cell proliferation, death, and morphology of human GBM cell lines and in primary human glial cultures, the normal cells from which GBM tumors arise. The influence of a plant derived cannabinoid agonist, Δ9-tetrahydrocannabinol Δ9-THC), and a potent synthetic cannabinoid agonist, WIN 55,212-2, were compared using time lapse microscopy. We discovered that Δ9-THC decreases cell proliferation and increases cell death of human GBM cells more rapidly than WIN 55,212-2. Δ9-THC was also more potent at inhibiting the proliferation of GBM cells compared to WIN 55,212-2. The effects of Δ9-THC and WIN 55,212-2 on the GBM cells were partially the result of cannabinoid receptor activation. The same concentration of Δ9-THC that significantly inhibits proliferation and increases death of human GBM cells has no significant impact on human primary glial cultures. Evidence of selective efficacy with WIN 55,212-2 was also observed but the selectivity was less profound, and the synthetic agonist produced a greater disruption of normal cell morphology compared to Δ9-THC.

Keywords

cannabinoid Delta-9-tetrahydrocannabinol extracellular signal regulated kinases glioblastma multiforme time lapse microscopy 

Abbreviations

CB

cannabinoid

ERK

extracellular signal regulated kinases

FBS

fetal bovine serum

GBM

glioblastoma multiforme

MANOVA

multivariate analysis of variance

MAPK

mitogen-activated protein kinases

Δ9-THC

Δ9-tetrahydrocannabinol

TLM

time lapse microscopy

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Copyright information

© Springer 2005

Authors and Affiliations

  • Sean D. Mc Allister
    • 1
  • Calvin Chan
    • 1
  • Ryan J. Taft
    • 1
  • Tri Luu
    • 1
  • Mary E. Abood
    • 1
  • Dan H. Moore
    • 1
    • 2
  • Ken Aldape
    • 3
  • Garret Yount
    • 1
  1. 1.California Pacific Medical Center Research InstituteSan FranciscoUSA
  2. 2.Department of Epidemiology and BiostatisticsUniversity of California San FranciscoSan FranciscoUSA
  3. 3.Department of PathologyUniversity of Texas MD Anderson Cancer CenterHoustonUSA

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