Cannabinoids inhibit cellular respiration of human oral cancer cells.
OBJECTIVE
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.


METHODS
A phosphorescence analyzer that measures the time-dependence of O(2) concentration in cellular or mitochondrial suspensions was used for this purpose.


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
These results show the cannabinoids are potent inhibitors of Tu183 cellular respiration and are toxic to this highly malignant tumor.
Department of Pediatricsy, State University of New York, Upstate Medical University, Syracuse, NY, USA.
Donna A
DA
Whyte
Suleiman
S
Al-Hammadi
Ghazala
G
Balhaj
Oliver M
OM
Brown
Harvey S
HS
Penefsky
Abdul-Kader
AK
Souid
D000255:Adenosine Triphosphate / Q000378:metabolism; D045744:Cell Line, Tumor; D019069:Cell Respiration / Q000187:drug effects*; D013759:Dronabinol / Q000031:analogs & derivatives* / Q000494:pharmacology*; D006801:Humans; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D009062:Mouth Neoplasms / Q000378:metabolism*; D010101:Oxygen Consumption / Q000187:drug effects
C035731:delta-8-tetrahydrocannabinol; D013759:Dronabinol; D000255:Adenosine Triphosphate