HU-210, a synthetic analog of ∆ 9 -THC, is not a modifier of estrogen signaling in MCF-7 human breast cancer cells

Abstract

— ∆ 9 -Tetrahydrocannabinol (∆ 9 -THC), an active ingredient of marijuana, evokes a number of biological effects including anti-cancer and anti-estrogenic actions. We and others have so far focused on and investigated the latter action. We recently reported that ∆ 9 -THC up-regulates the expression of estrogen receptor β (ERβ, ESR2), resulting in the abrogation of 17β-estradiol (E2)-mediated ERα signal-ing (Takeda et al., Chem. Res. Toxicol., 26, 1073-1079, 2013). This finding may shed light on the possi-ble endocrine-disrupting mechanism(s) employed by cannabinoids including ∆ 9 -THC. Although previous studies have suggested that HU-210, a synthetic analog of ∆ 9 -THC, evokes a set of endocrine altera-tions closely related to those of ∆ 9 -THC, none have examined the effects of cannabinoids with a focus on the expression of ERβ, a " suppressive " molecule for ERα-mediated signaling. Thus, we herein deter-mined whether HU-210 is also an endocrine modifier similar to ∆ 9 -THC using ERα-positive MCF-7 cells in which the expression of ERβ is maintained at very low levels. The results of the present study revealed that HU-210, despite having a similar structure to ∆ 9 -THC, did not modulate E2/ERα signaling or induce ERβ.