Delta9-Tetrahydrocannabinol, a major component of marijuana, disrupts estrogen-signaling through estrogen receptor beta

2015 Fiscal Year Final Research Report

• Project/Area Number: 25460182
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Environmental and hygienic pharmacy
• Research Institution: Hiroshima International University
• Principal Investigator: Takeda Shuso 広島国際大学, 薬学部, 准教授 (00460379)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Keywords: テトラヒドロカンナビノール / 薬物型大麻草 / 内分泌かく乱 / ERβ / 乳がん

Outline of Final Research Achievements

Is Δ9-tetrahydrocannabinol (Δ9-THC) an anti-estrogenic chemical? Since Δ9-THC is used both recreationally and medicinally for the treatment of pain and nausea in cancer patients undergoing chemotherapy in the United States and other countries, it is important to investigate the mechanistic basis of Δ9-THC’s 17β-estradiol (E2) signaling disruption. By using estrogen receptor α (ERα)-positive human breast cancer cell line MCF-7, we report here that Δ9-THC’s growth suppressive effects on MCF-7 cells are drastically seen in the presence of E2, and that Δ9-THC inhibits E2-stimulated ERα activation, leading to cell growth. Mechanistically, by performing several lines of biochemical analyses, it is demonstrated that i) Δ9-THC up-regulates ERβ, being recognized as a repressor of ERα function and ii) Δ9-THC function as an activator for the ERβ to interfere with ERα. The data here suggest that anti-estrogenic Δ9-THC disrupts E2/ERα signaling via the second type of ER, ERβ.

Free Research Field

分子毒性学