β-Thujaplicin Suppressed Estrogen Receptor Negative Mammary Tumor Growth and Regulated the Cell Cycle Progression

초록

β-Thujaplicin (Hinokitiol), a natural monoterpenoid, identified in Chamaecyparis obtusa has been demonstrated to exert anti-inflammatory, anti-bacterial, anti-oxidant and anti-tumor activities. However, the effect of β-thujaplicin on breast cancer has not been extensively studied. In the present study, β-thujaplicin significantly inhibited the proliferation of estrogen receptor(ER) negative MCF10DCIS.com human breast cancer cells in a dose dependent manner. In flow cytometry, β-thujaplicin enhanced the accumulation of G0/G1 phase as well as the reduction of S phase, and down-regulated the expression of cell cycle mediators in G0/G1 phase including cyclin D1, cyclin E, cyclin dependent kinase 4 (CDK 4), indicating that transition from G0/G1 to S phase is suppressed by β-thujaplicin treatment. In the xenograpt animal model of MCF10DCIS.com cells, β-thujaplicin treatment intraperitioneally at 1mg/kg body weight reduced tumor growth and tumor weight and was confirmed to inhibit the expression of cyclin D1, cyclin E and CDK 4 in tumor tissues. These results demonstrated that a natural β-thujaplicin suppressed the ER negative tumor growth, which may be derived from G0/G1 arrest, and suggest that β-thujaplicin can be considered as a potent chemopreventive agent in ER negative breast cancer.