Down-regulation of cyclooxygenase-2 (COX-2) by cannabidiolic acid in human breast cancer cells

作者：Takeda Shuso; Okazaki Hiroyuki; Ikeda Eriko; Abe Satomi; Yoshioka Yasushi; Watanabe Kazuhito; Aramaki Hironori^*

来源：Journal of Toxicological Sciences, 2014, 39(5): 711-716.

DOI：10.2131/jts.39.711

• Cannabidiolic acid
• Cyclooxygenase-2
• Human breast cancer cells
• Fiber-type cannabis plant
• Metastasis

Metastases are known to be responsible for approximately 90% of breast cancer-related deaths. Cyclooxygenase-2 (COX-2) is involved not only in inflammatory processes, but also in the metastasis of cancer cells; it is expressed in 40% of human invasive breast cancers. To comprehensively analyze the effects of cannabidiolic acid (CBDA), a selective COX-2 inhibitor found in the fiber-type cannabis plant (Takeda et al., 2008), on COX-2 expression and the genes involved in metastasis, we performed a DNA microarray analysis of human breast cancer MDA-MB-231 cells, which are invasive breast cancer cells that express high levels of COX-2, treated with CBDA for 48 hr at 25 mu M. The results obtained revealed that COX-2 and Id-1, a positive regulator of breast cancer metastasis, were down-regulated (0.19-fold and 0.52-fold, respectively), while SHARP1 (or BHLHE41), a suppressor of breast cancer metastasis, was up-regulated (1.72-fold) and CHIP (or STUB 1) was unaffected (1.03-fold). These changes were confirmed by real-time RT-PCR analyses. Taken together, the results obtained here demonstrated that i) CBDA had dual inhibitory effects on COX-2 through down-regulation and enzyme inhibition, and ii) CBDA may possess the ability to suppress genes that are positively involved in the metastasis of cancer cells in vitro.

• 出版日期2014-10