Abstract
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.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 18-24 |
| Number of pages | 7 |
| Journal | Toxicology |
| Volume | 326 |
| DOIs | |
| State | Published - Dec 4 2014 |
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All Science Journal Classification (ASJC) codes
- Toxicology
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δ9-THC modulation of fatty acid 2-hydroxylase (FA2H) gene expression : Possible involvement of induced levels of PPARα in MDA-MB-231 breast cancer cells. / Takeda, Shuso; Ikeda, Eriko; Su, Shengzhong; Harada, Mari; Okazaki, Hiroyuki; Yoshioka, Yasushi; Nishimura, Hajime; Ishii, Hiroyuki; Kakizoe, Kazuhiro; Taniguchi, Aya; Tokuyasu, Miki; Himeno, Taichi; Watanabe, Kazuhito; Omiecinski, Curtis J.; Aramaki, Hironori.
In: Toxicology, Vol. 326, 04.12.2014, p. 18-24.Research output: Contribution to journal › Article
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
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 -