Abstract 4226: B-thujaplicin suppressed estrogen dependent breast cancer via regulating estrogen receptor signaling

Abstract

Abstract B-thujaplicin (Hinokitiol), a natural monoterpenoid found in the family of Chamaecyparis obtusa, has been demonstrated to exert anti-fungal, anti-bacterial, and anti-oxidant properties. However, the role of β-thujaplicin in mammary carcinogenesis has not been extensively studied. Here, we investigated the effect of β-thujaplicin on cell proliferation and underlying mechanisms in estrogen-dependent MCF-7 breast cancer cells and N-nitroso methy urea (NMU)-induced animal model. We first found that β-thujaplicin inhibited cell proliferation in a dose dependent manner, where the IC50 was 7.5 μM. The protein and mRNA expression of estrogen receptor (ER)-α was suppressed by β-thujaplicin, without affecting the level of ER-β. One of the target genes of estrogen signaling, cyclin D1 was also significantly inhibited by β-thujaplicin treatment. In animal study of NMU-induced breast cancer model, β-thujaplicin at 7.5mg/kg body weight significantly suppressed tumor growth and tumor multiplicity from 3.1 g in the control to 1.8 g in the β-thujaplicin treatment group, and from 2.9 tumor/rat to 1.7 tumor/rat, respectively. The ER-α expression and cyclin D1 in tumor tissues were also reduced by β-thujaplicin treatment. Taken together, β-thujaplicin suppressed ER-positive breast carcinogenesis through suppressing the ER-α expression and its target gene cyclin D1, and it suggests that β-thujaplicin may be a potent phytochemical in inhibiting breast cancer development. Citation Format: Jiwon Ko, Cheng Bao, Jaehoo Lee, Hyun-Chang Park, Hong Jin Lee. B-thujaplicin suppressed estrogen dependent breast cancer via regulating estrogen receptor signaling. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 4226. doi:10.1158/1538-7445.AM2014-4226