title: Induction of the fatty acid 2-hydroxylase (FA2H) gene by Δ(9)-tetrahydrocannabinol in human breast cancer cells.
abstract: To investigate gene(s) being regulated by ∆(9)-tetrahydrocannabinol (∆(9)-THC), we performed DNA microarray analysis of human breast cancer MDA-MB-231 cells, which are poorly differentiated breast cancer cells, treated with ∆(9)-THC for 48 hr at an IC50 concentration of approximately 25 µM. Among the highly up-regulated genes (> 10-fold) observed, fatty acid 2-hydroxylase (FA2H) was significantly induced (17.8-fold). Although the physiological role of FA2H has not yet been fully understood, FA2H has been shown to modulate cell differentiation. The results of Oil Red O staining after ∆(9)-THC exposure showed the distribution of lipid droplets (a sign of the differentiated phenotype) in cells. Taken together, the results obtained here indicate that FA2H is a novel ∆(9)-THC-regulated gene, and that ∆(9)-THC induces differentiation signal(s) in poorly differentiated MDA-MB-231 cells.
authors.affiliation: Department of Molecular Biology, Daiichi University of Pharmacy, Fukuoka, Japan.
authors.forename: Shuso
authors.initials: S
authors.lastname: Takeda
authors.forename: Mari
authors.initials: M
authors.lastname: Harada
authors.forename: Shengzhong
authors.initials: S
authors.lastname: Su
authors.forename: Shunsuke
authors.initials: S
authors.lastname: Okajima
authors.forename: Hiroko
authors.initials: H
authors.lastname: Miyoshi
authors.forename: Kazutaka
authors.initials: K
authors.lastname: Yoshida
authors.forename: Hajime
authors.initials: H
authors.lastname: Nishimura
authors.forename: Yoshiko
authors.initials: Y
authors.lastname: Okamoto
authors.forename: Toshiaki
authors.initials: T
authors.lastname: Amamoto
authors.forename: Kazuhito
authors.initials: K
authors.lastname: Watanabe
authors.forename: Curtis J
authors.initials: CJ
authors.lastname: Omiecinski
authors.forename: Hironori
authors.initials: H
authors.lastname: Aramaki
mesh_terms: D001943:Breast Neoplasms / Q000235:genetics* / Q000473:pathology; D002454:Cell Differentiation / Q000187:drug effects; D013759:Dronabinol / Q000494:pharmacology*; D005260:Female; D006801:Humans; D006899:Mixed Function Oxygenases / Q000235:genetics* / Q000502:physiology; D020411:Oligonucleotide Array Sequence Analysis; D047493:PPAR alpha / Q000502:physiology; D012333:RNA, Messenger / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015533:Transcriptional Activation / Q000187:drug effects*; D014407:Tumor Cells, Cultured; D015854:Up-Regulation
chemical_list: D047493:PPAR alpha; D012333:RNA, Messenger; D013759:Dronabinol; D006899:Mixed Function Oxygenases; C019081:fatty acid alpha-hydroxylase
references.citation: Mol Endocrinol. 2008 Oct;22(10):2215-28
references.pmid: 18417735
references.citation: J Toxicol Sci. 2011;36(6):843-5
references.pmid: 22129749
references.citation: Chem Res Toxicol. 2011 Jun 20;24(6):855-65
references.pmid: 21568272
references.citation: Biochem Biophys Res Commun. 2005 Nov 25;337(3):824-31
references.pmid: 16213464
references.citation: J Toxicol Sci. 2011 Jun;36(3):389-91
references.pmid: 21628967
references.citation: Pharmacol Rev. 2010 Dec;62(4):588-631
references.pmid: 21079038
references.citation: Chem Pharm Bull (Tokyo). 1968 May;16(5):822-6
references.pmid: 5728171
references.citation: Drug Metab Dispos. 2008 Sep;36(9):1917-21
references.pmid: 18556441
references.citation: Nat Rev Cancer. 2012 Feb 09;12(3):181-95
references.pmid: 22318237
references.citation: Biochim Biophys Acta. 2010 Apr;1801(4):405-14
references.pmid: 20026285