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Therapeutic potential of cannabinoid-based compounds for the treatment of brain cancer: Anti-tumor efficacy in glioblastoma multiform

A novel series of anti-tumor drug for the treatment of brain cancers

 

Human clinical trials show that cannabidiol, a non-psychotropic plant-derived cannabinoid compound, exhibits significant therapeutic efficacy for the treatment of young adults suffering from seizures, including the devastating refractory seizures that develop in Dravet Syndrome. The Stella laboratory studies the molecular and cellular mechanism of action (MOA) of cannabinoid-based compounds with the goal of optimizing their therapeutic efficacy while minimizing side-effects and toxicity profiles.

In 2010, we started to explore the mechanism of action (MOA) and therapeutic value of cannabinoid-based compound for the treatment of glioblastoma multiform (GBM). We confirmed that cannabinoid-based compounds that act through CB1 and CB2 receptors trigger apoptosis in GBM cells and discovered that a considerable proportion of the anti-tumor activity of cannabinoid-based compounds is mediated through an unknown MOA.

Text Box:    Indole-based compounds act at multiple targets

We developed indole-based compounds that do not activate CB1 and CB2 receptors and yet kill GBM cells by destabilizing microtubules, a fundamental enzymatic machinery that controls cell migration, proliferation and viability of cancer cells. Recent medicinal chemistry efforts led to the development of novel analogues of indole-based compounds that exhibit nanomolar activity at destabilizing microtubules and killing GBM cells.

Our current efforts focus on better understanding the MOA of cannabinoid-based and indole-based compounds acting through cannabinoid receptors and microtubules and the signaling pathways leading to cell death, to further the preclinical development of this new class of anti-tumor therapeutics.

Our hope is that this new class of anti-tumor compounds will rapidly become a new therapeutic modality for the safe treatment of brain cancers, including GBM.

Text Box:    Indole-based compounds trigger chromosome lingering in glioblastoma cells
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Updated 9/20/2017