Delta(9)-Tetrahydrocannabinol upregulates fatty acid 2-hydroxylase (FA2H) via PPAR alpha induction: A possible evidence for the cancellation of PPAR beta/delta-mediated inhibition of PPAR alpha in MDA-MB-231 cells

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作   者：

Hirao-Suzuki, Masayo;  Takeda, Shuso;  Watanabe, Kazuhito;  Takiguchi, Masufumi;  Aramaki, Hironori; 

作者机构：

Fac Pharmaceut Sci;  Dept Mol Biol;  Hiroshima Int Univ;  Ctr Supporting Pharmaceut Educ;  5-1-1 Hirokoshingai;  Hiroshima 7370112;  Daiichi Univ Pharm;  Japan;  Minami Ku;  22-1 Tamagawa Cho;  Fukuoka;  Lab Xenobiot Metab & Environm Toxicol;  Kure;  Fukuoka 8158511; 

关键词：

Fatty acid 2-hydroxylase;  Delta(9)-Tetrahydrocannabinol;  Peroxisome proliferator-activated receptor alpha;  MDA-MB-231 cells; 

期刊名称：

Archives of Biochemistry and Biophysics

i s s n：

0003-9861

年卷期：

2019 年 662 卷

页   码：

219-225

页   码：

摘   要：

Peroxisome proliferator-activated receptors (PPARs) are a family of ligand-activated nuclear transcription factors, with three characterized subtypes: PPAR alpha, PPAR beta/delta, and PPAR gamma. The biological correlation between the two PPAR subtypes PPAR alpha and gamma and carcinogenesis is well-characterized; however, substantially less is known about the biological functions of PPAR beta/delta. PPAR beta/delta has been reported to repress transcription when PPAR beta/delta and PPAR alpha or PPAR gamma are simultaneously expressed in some cells, and MDA-MB-231 cells express functional levels of PPAR beta/delta. We have previously reported that Delta(9)-tetrahydrocannabinol (Delta(9)-THC), a major cannabinoid component of the drug-type cannabis plant, can stimulate the expression of fatty acid 2-hydroxylase (FA2H) via upregulation of PPAR alpha expression in human breast cancer MDA-MB-231 cells. Although the possibility of an inhibitory interaction between PPAR alpha and PPAR beta/delta has not been demonstrated in MDA-MB-231 cells, we reasoned if this interaction were to exist, Delta(9)-THC should make PPAR alpha free to achieve FA2H induction. Here, we show that a PPAR beta/delta-mediated suppression of PPAR alpha function, but not of PPAR gamma, exists in MDA-MB-231 cells and Delta(9)-THC causes FA2H induction via mechanisms underlying the cancellation of PPAR beta/delta-mediated inhibition of PPARa, in addition to the upregulation of PPAR alpha.