β-Thujaplicin modulates estrogen receptor signaling and inhibits proliferation of human breast cancer cells

beta-Thujaplicin, one of the major constituents in Chamaecyparis obtusa, has been demonstrated to exert different health beneficial efficacy, but the role of beta-thujaplicin in regulating mammary tumorigenesis has not been investigated. In this study, we found that beta-thujaplicin significantly suppressed the proliferation through arresting the cell cycle transition from G1 to S phase as well as inhibited the expression of cell cycle-related proteins, cyclin D1, and cyclin-dependent kinase 4 (CDK4) in MCF-7 and T47D luminal subtype breast cancer cells. In addition, estrogen receptor alpha (ER-alpha) was down-regulated by beta-thujaplicin via enhanced proteolysis by ubiquitination, which led to cell growth inhibition. These results suggest that beta-thujaplicin may be considered as a potent agent regulating the hormone sensitive mammary tumorigenesis.