Abstract
BACKGROUND AND PURPOSE:
The
primary cannabinoids, Delta(9)-tetrahydrocannabinol (Delta(9)-THC) and
Delta(8)-tetrahydrocannabinol (Delta(8)-THC) are known to disturb the
mitochondrial function and possess antitumor activities. These
observations prompted us to investigate their effects on the
mitochondrial O(2) 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 Delta(9)-THC or Delta(8)-THC was added to
the cells. The inhibition was concentration-dependent, and Delta(9)-THC
was the more potent of the two compounds. Anandamide (an
endocannabinoid) was ineffective; suggesting the effects of Delta(9)-THC
and Delta(8)-THC were not mediated by the cannabinoidreceptors.
Inhibition of O(2) consumption by cyanide confirmed the oxidations
occurred in the mitochondrial respiratory chain. Delta(9)-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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