TY - JOUR
T1 - δ9-THC modulation of fatty acid 2-hydroxylase (FA2H) gene expression
T2 - Possible involvement of induced levels of PPARα in MDA-MB-231 breast cancer cells
AU - Takeda, Shuso
AU - Ikeda, Eriko
AU - Su, Shengzhong
AU - Harada, Mari
AU - Okazaki, Hiroyuki
AU - Yoshioka, Yasushi
AU - Nishimura, Hajime
AU - Ishii, Hiroyuki
AU - Kakizoe, Kazuhiro
AU - Taniguchi, Aya
AU - Tokuyasu, Miki
AU - Himeno, Taichi
AU - Watanabe, Kazuhito
AU - Omiecinski, Curtis J.
AU - Aramaki, Hironori
N1 - Funding Information:
This study was supported in part by a Grant-in-Aid for Scientific Research (C) [25,460,182, (to S.T.)] and in part by a Grant-in-Aid for Young Scientists (Start-up) [25,893,282, (to E.I.)] from the Japan Society for the Promotion of Science (JSPS) KAKENHI. C.J.O. was supported by a USPHS award, ES016358.
Publisher Copyright:
© 2014 Elsevier Ireland Ltd.
PY - 2014/12/4
Y1 - 2014/12/4
N2 - We recently reported that δ9-tetrahydrocannabinol (δ9-THC), a major cannabinoid component in Cannabis Sativa (marijuana), significantly stimulated the expression of fatty acid 2-hydroxylase (FA2H) in human breast cancer MDA-MB-231 cells. Peroxisome proliferator-activated receptor α (PPARα) was previously implicated in this induction. However, the mechanisms mediating this induction have not been elucidated in detail. We performed a DNA microarray analysis of δ9-THC-treated samples and showed the selective up-regulation of the PPARα isoform coupled with the induction of FA2H over the other isoforms (β and γ). δ9-THC itself had no binding/activation potential to/on PPARα, and palmitic acid (PA), a PPARα ligand, exhibited no stimulatory effects on FA2H in MDA-MB-231 cells; thus, we hypothesized that the levels of PPARα induced were involved in the δ9-THC-mediated increase in FA2H. In support of this hypothesis, we herein demonstrated that; (i) δ9-THC activated the basal transcriptional activity of PPARα in a concentration-dependent manner, (ii) the concomitant up-regulation of PPARα/FA2H was caused by δ9-THC, (iii) PA could activate PPARα after the PPARα expression plasmid was introduced, and (iv) the δ9-THC-induced up-regulation of FA2H was further stimulated by the co-treatment with L-663,536 (a known PPARα inducer). Taken together, these results support the concept that the induced levels of PPARα may be involved in the δ9-THC up-regulation of FA2H in MDA-MB-231 cells.
AB - We recently reported that δ9-tetrahydrocannabinol (δ9-THC), a major cannabinoid component in Cannabis Sativa (marijuana), significantly stimulated the expression of fatty acid 2-hydroxylase (FA2H) in human breast cancer MDA-MB-231 cells. Peroxisome proliferator-activated receptor α (PPARα) was previously implicated in this induction. However, the mechanisms mediating this induction have not been elucidated in detail. We performed a DNA microarray analysis of δ9-THC-treated samples and showed the selective up-regulation of the PPARα isoform coupled with the induction of FA2H over the other isoforms (β and γ). δ9-THC itself had no binding/activation potential to/on PPARα, and palmitic acid (PA), a PPARα ligand, exhibited no stimulatory effects on FA2H in MDA-MB-231 cells; thus, we hypothesized that the levels of PPARα induced were involved in the δ9-THC-mediated increase in FA2H. In support of this hypothesis, we herein demonstrated that; (i) δ9-THC activated the basal transcriptional activity of PPARα in a concentration-dependent manner, (ii) the concomitant up-regulation of PPARα/FA2H was caused by δ9-THC, (iii) PA could activate PPARα after the PPARα expression plasmid was introduced, and (iv) the δ9-THC-induced up-regulation of FA2H was further stimulated by the co-treatment with L-663,536 (a known PPARα inducer). Taken together, these results support the concept that the induced levels of PPARα may be involved in the δ9-THC up-regulation of FA2H in MDA-MB-231 cells.
UR - http://www.scopus.com/inward/record.url?scp=84908127350&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84908127350&partnerID=8YFLogxK
U2 - 10.1016/j.tox.2014.09.011
DO - 10.1016/j.tox.2014.09.011
M3 - Article
C2 - 25291031
AN - SCOPUS:84908127350
VL - 326
SP - 18
EP - 24
JO - Toxicology
JF - Toxicology
SN - 0300-483X
ER -