Abstract
We recently reported that Δ{sup 9}-tetrahydrocannabinol (Δ{sup 9}-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 Δ{sup 9}-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). Δ{sup 9}-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 Δ{sup 9}-THC-mediated increase in FA2H. In support of this hypothesis, we herein demonstrated that; (i) Δ{sup 9}-THC activated the basal transcriptional activity of PPARα in a concentration-dependent manner, (ii) the concomitant up-regulation of PPARα/FA2H was caused by Δ{sup 9}-THC, (iii) PA could activate PPARα after the PPARα expression plasmid was introduced, and (iv) the Δ{sup 9}-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
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Takeda, Shuso;
[1]
Laboratory of Xenobiotic Metabolism and Environmental Toxicology, Faculty of Pharmaceutical Sciences, Hiroshima International University (HIU), 5-1-1 Hiro-koshingai, Kure, Hiroshima 737-0112 (Japan)];
Ikeda, Eriko;
[1]
Su, Shengzhong;
[2]
Harada, Mari;
[1]
Okazaki, Hiroyuki;
[3]
Yoshioka, Yasushi;
Nishimura, Hajime;
Ishii, Hiroyuki;
Kakizoe, Kazuhiro;
Taniguchi, Aya;
Tokuyasu, Miki;
Himeno, Taichi;
[1]
Watanabe, Kazuhito;
[4]
Omiecinski, Curtis J.;
[2]
Aramaki, Hironori;
[1]
Drug Innovation Research Center, Daiichi University of Pharmacy, 22-1 Tamagawa-cho, Minami-ku, Fukuoka 815-8511 (Japan)]
- Department of Molecular Biology, Daiichi University of Pharmacy, 22-1 Tamagawa-cho, Minami-ku, Fukuoka 815-8511 (Japan)
- Center for Molecular Toxicology and Carcinogenesis, 101 Life Sciences Building, Pennsylvania State University, University Park, PA 16802 (United States)
- Drug Innovation Research Center, Daiichi University of Pharmacy, 22-1 Tamagawa-cho, Minami-ku, Fukuoka 815-8511 (Japan)
- Department of Hygienic Chemistry, Faculty of Pharmaceutical Sciences, Hokuriku University, Ho-3 Kanagawa-machi, Kanazawa 920-1181 (Japan)
Citation Formats
Takeda, Shuso, Laboratory of Xenobiotic Metabolism and Environmental Toxicology, Faculty of Pharmaceutical Sciences, Hiroshima International University (HIU), 5-1-1 Hiro-koshingai, Kure, Hiroshima 737-0112 (Japan)], 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, and Drug Innovation Research Center, Daiichi University of Pharmacy, 22-1 Tamagawa-cho, Minami-ku, Fukuoka 815-8511 (Japan)].
Δ{sup 9}-THC modulation of fatty acid 2-hydroxylase (FA2H) gene expression: Possible involvement of induced levels of PPARα in MDA-MB-231 breast cancer cells.
Ireland: N. p.,
2014.
Web.
doi:10.1016/J.TOX.2014.09.011.
Takeda, Shuso, Laboratory of Xenobiotic Metabolism and Environmental Toxicology, Faculty of Pharmaceutical Sciences, Hiroshima International University (HIU), 5-1-1 Hiro-koshingai, Kure, Hiroshima 737-0112 (Japan)], 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, & Drug Innovation Research Center, Daiichi University of Pharmacy, 22-1 Tamagawa-cho, Minami-ku, Fukuoka 815-8511 (Japan)].
Δ{sup 9}-THC modulation of fatty acid 2-hydroxylase (FA2H) gene expression: Possible involvement of induced levels of PPARα in MDA-MB-231 breast cancer cells.
Ireland.
https://doi.org/10.1016/J.TOX.2014.09.011
Takeda, Shuso, Laboratory of Xenobiotic Metabolism and Environmental Toxicology, Faculty of Pharmaceutical Sciences, Hiroshima International University (HIU), 5-1-1 Hiro-koshingai, Kure, Hiroshima 737-0112 (Japan)], 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, and Drug Innovation Research Center, Daiichi University of Pharmacy, 22-1 Tamagawa-cho, Minami-ku, Fukuoka 815-8511 (Japan)].
2014.
"Δ{sup 9}-THC modulation of fatty acid 2-hydroxylase (FA2H) gene expression: Possible involvement of induced levels of PPARα in MDA-MB-231 breast cancer cells."
Ireland.
https://doi.org/10.1016/J.TOX.2014.09.011.
@misc{etde_22438522,
title = {Δ{sup 9}-THC modulation of fatty acid 2-hydroxylase (FA2H) gene expression: Possible involvement of induced levels of PPARα in MDA-MB-231 breast cancer cells}
author = {Takeda, Shuso, Laboratory of Xenobiotic Metabolism and Environmental Toxicology, Faculty of Pharmaceutical Sciences, Hiroshima International University (HIU), 5-1-1 Hiro-koshingai, Kure, Hiroshima 737-0112 (Japan)], 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, and Drug Innovation Research Center, Daiichi University of Pharmacy, 22-1 Tamagawa-cho, Minami-ku, Fukuoka 815-8511 (Japan)]}
abstractNote = {We recently reported that Δ{sup 9}-tetrahydrocannabinol (Δ{sup 9}-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 Δ{sup 9}-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). Δ{sup 9}-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 Δ{sup 9}-THC-mediated increase in FA2H. In support of this hypothesis, we herein demonstrated that; (i) Δ{sup 9}-THC activated the basal transcriptional activity of PPARα in a concentration-dependent manner, (ii) the concomitant up-regulation of PPARα/FA2H was caused by Δ{sup 9}-THC, (iii) PA could activate PPARα after the PPARα expression plasmid was introduced, and (iv) the Δ{sup 9}-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 Δ{sup 9}-THC up-regulation of FA2H in MDA-MB-231 cells.}
doi = {10.1016/J.TOX.2014.09.011}
journal = []
volume = {326}
journal type = {AC}
place = {Ireland}
year = {2014}
month = {Dec}
}
title = {Δ{sup 9}-THC modulation of fatty acid 2-hydroxylase (FA2H) gene expression: Possible involvement of induced levels of PPARα in MDA-MB-231 breast cancer cells}
author = {Takeda, Shuso, Laboratory of Xenobiotic Metabolism and Environmental Toxicology, Faculty of Pharmaceutical Sciences, Hiroshima International University (HIU), 5-1-1 Hiro-koshingai, Kure, Hiroshima 737-0112 (Japan)], 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, and Drug Innovation Research Center, Daiichi University of Pharmacy, 22-1 Tamagawa-cho, Minami-ku, Fukuoka 815-8511 (Japan)]}
abstractNote = {We recently reported that Δ{sup 9}-tetrahydrocannabinol (Δ{sup 9}-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 Δ{sup 9}-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). Δ{sup 9}-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 Δ{sup 9}-THC-mediated increase in FA2H. In support of this hypothesis, we herein demonstrated that; (i) Δ{sup 9}-THC activated the basal transcriptional activity of PPARα in a concentration-dependent manner, (ii) the concomitant up-regulation of PPARα/FA2H was caused by Δ{sup 9}-THC, (iii) PA could activate PPARα after the PPARα expression plasmid was introduced, and (iv) the Δ{sup 9}-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 Δ{sup 9}-THC up-regulation of FA2H in MDA-MB-231 cells.}
doi = {10.1016/J.TOX.2014.09.011}
journal = []
volume = {326}
journal type = {AC}
place = {Ireland}
year = {2014}
month = {Dec}
}