Induction of the fatty acid 2-hydroxylase (FA2H) gene by Δ9-tetrahydrocannabinol in human breast cancer cells

• Published in: Journal of toxicological sciences 2013/04/01, Vol.38(2), pp.305-308
• Main Authors: Takeda, Shuso, Harada, Mari, Su, Shengzhong, Okajima, Shunsuke, Miyoshi, Hiroko, Yoshida, Kazutaka, Nishimura, Hajime, Okamoto, Yoshiko, Amamoto, Toshiaki, Watanabe, Kazuhito, Omiecinski, Curtis J, Aramaki, Hironori
• Format: Article
• Language: English
• Subjects: Differentiation; Fatty acid 2-hydroxylase; PPARα human breast cancer cells; Δ9-tetrahydrocannabinol
• ISSN: 0388-1350; 1880-3989
• DOI: 10.2131/jts.38.305

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.