Cannabinoids inhibit cellular respiration of human oral cancer cells

Donna A. Whyte, Suleiman Al-Hammadi, Ghazala Balhaj, Oliver M. Brown, Harvey S. Penefsky, Abdul Kader Souid

Research output: Contribution to journalArticlepeer-review

Abstract

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 O 2 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.

Original languageEnglish (US)
Pages (from-to)328-335
Number of pages8
JournalPharmacology
Volume85
Issue number6
DOIs
StatePublished - Jul 2010
Externally publishedYes

Keywords

  • Cannabinoids
  • Mitochondria
  • Oral cancer
  • Respiration

ASJC Scopus subject areas

  • Pharmacology

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