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Vol. 85, No. 6, 2010
Issue release date: July 2010
Pharmacology 2010;85:328–335

Cannabinoids Inhibit Cellular Respiration of Human Oral Cancer Cells

Whyte D.A. · Al-Hammadi S. · Balhaj G. · Brown O.M. · Penefsky H.S. · Souid A.-K.
Departments of aPediatrics and bPharmacology, State University of New York, Upstate Medical University, Syracuse, N.Y., and cPublic Health Research Institute, New Jersey, N.J., USA; dDepartment of Pediatrics, United Arab Emirates University, Faculty of Medicine and Health Sciences, Al Ain, United Arab Emirates

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Background and Purpose: The primary cannabinoids, Δ9-tetrahydrocannabinol (Δ9-THC) and Δ8-tetrahydrocannabinol (Δ8-THC) are known to disturb the mitochondrial function and possess antitumor activities. These observations prompted us to investigate their effects on the mitochondrial O2 consumption in human oral cancer cells (Tu183). This epithelial cell line overexpresses bcl-2 and is highly resistant to anticancer drugs. Experimental Approach: A phosphorescence analyzer that measures the time-dependence of O2 concentration in cellular or mitochondrial suspensions was used for this purpose. Key Results: A rapid decline in the rate of respiration was observed when Δ9-THC or Δ8-THC was added to the cells. The inhibition was concentration-dependent, and Δ9-THC was the more potent of the two compounds. Anandamide (an endocannabinoid) was ineffective; suggesting the effects of Δ9-THC and Δ8-THC were not mediated by the cannabinoidreceptors. Inhibition of O2 consumption by cyanide confirmed the oxidations occurred in the mitochondrial respiratory chain. Δ9-THC inhibited the respiration of isolated mitochondria from beef heart. Conclusions and Implications: These results show the cannabinoids are potent inhibitors of Tu183 cellular respiration and are toxic to this highly malignant tumor.

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