Delta(9)-Tetrahydrocannabinol enhances MCF-7 cell proliferation via cannabinoid receptor-independent signaling.
We recently reported that Delta(9)-tetrahydrocannabinol (Delta(9)-THC) has the ability to stimulate the proliferation of human breast carcinoma MCF-7 cells. However, the mechanism of action remains to be clarified. The present study focused on the relationship between receptor expression and the effects of Delta(9)-THC on cell proliferation. RT-PCR analysis demonstrated that there was no detectable expression of CB receptors in MCF-7 cells. In accordance with this, no effects of cannabinoid 1/2 (CB1/2) receptor antagonists and pertussis toxin on cell proliferation were observed. Although MCF-7 cell proliferation is suggested to be suppressed by Delta(9)-THC in the presence of CB receptors, it was revealed that Delta(9)-THC could exert upregulation of living cells in the absence of the receptors. Interestingly, Delta(9)-THC upregulated human epithelial growth factor receptor type 2 (HER2) expression, which is known to be a predictive factor of human breast cancer and is able to stimulate cancer cells as well as MCF-7 cells. Actinomycin D-treatment interfered with the upregulation of HER2 and cell proliferation by cannabinoid. Taken together, these studies suggest that, in the absence of CB receptors, Delta(9)-THC can stimulate the proliferation of MCF-7 cells by modulating, at least in part, HER2 transcription.
Takeda
Shuso
S
Organization for Frontier Research in Preventive Pharmaceutical Sciences, Hokuriku University, Ho-3 Kanagawa-machi, Kanazawa 920-1181, Japan.
Yamaori
Satoshi
S
Motoya
Erina
E
Matsunaga
Tamihide
T
Kimura
Toshiyuki
T
Yamamoto
Ikuo
I
Watanabe
Kazuhito
K
D000199:Actins / Q000378:metabolism; D000581:Amidohydrolases / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D013759:Dronabinol / Q000494:pharmacology*; D006801:Humans; D043884:Receptor, Cannabinoid, CB1 / Q000037:antagonists & inhibitors / Q000378:metabolism; D043885:Receptor, Cannabinoid, CB2 / Q000037:antagonists & inhibitors / Q000378:metabolism; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism; D043882:Receptors, Cannabinoid / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000187:drug effects*; D000099252:Fatty Acid Amide Hydrolases
D000199:Actins; D000581:Amidohydrolases; D013759:Dronabinol; D043884:Receptor, Cannabinoid, CB1; D043885:Receptor, Cannabinoid, CB2; D018719:Erb-b2 Receptor Tyrosine Kinases; D043882:Receptors, Cannabinoid; D000099252:Fatty Acid Amide Hydrolases