Δ9-tetrahydrocannabinol disrupts estrogen-signaling through up-regulation of estrogen receptor β (ERβ)

Shuso Takeda, Kazutaka Yoshida, Hajime Nishimura, Mari Harada, Shunsuke Okajima, Hiroko Miyoshi, Yoshiko Okamoto, Toshiaki Amamoto, Kazuhito Watanabe, Curtis J. Omiecinski, Hironori Aramaki

Research output: Contribution to journalArticlepeer-review

27 Scopus citations

Abstract

Δ9-Tetrahydrocannabinol (Δ9-THC) has been reported as possessing antiestrogenic activity, although the mechanisms underlying these effects are poorly delineated. In this study, we used the estrogen receptor α (ERα)-positive human breast cancer cell line, MCF-7, as an experimental model and showed that Δ9-THC exposures markedly suppresses 17β-estradiol (E2)- induced MCF-7 cell proliferation. We demonstrate that these effects result from Δ9-THC's ability to inhibit E2-liganded ERα activation. Mechanistically, the data obtained from biochemical analyses revealed that (i) Δ9-THC up-regulates ERβ, a repressor of ERα, inhibiting the expression of E2/ERα-regulated genes that promote cell growth and that (ii) Δ9-THC induction of ERβ modulates E2/ERα signaling in the absence of direct interaction with the E2 ligand binding site. Therefore, the data presented support the concept that Δ9-THC's antiestrogenic activities are mediated by the ERβ disruption of E2/ERα signaling.

Original languageEnglish (US)
Pages (from-to)1073-1079
Number of pages7
JournalChemical research in toxicology
Volume26
Issue number7
DOIs
StatePublished - Jul 15 2013

All Science Journal Classification (ASJC) codes

  • Toxicology

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