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Induction of G1 arrest and differentiation in MDA-MB-231 breast cancer cell by boehmeriasin A, a novel compound from plant
  1. J. Yan*,
  2. D. Luo*,
  3. Y. Luo,
  4. X. Gao* and
  5. G. Zhang
  1. *Institute of materia medica, Di Ao Pharmaceutical Group, Chengdu, People's Republic of China
  2. Chengdu Institute of Biology, The Chinese Academy of Sciences, Chengdu, People's Republic of China
  1. Address correspondence and reprint requests to: Xiaoping Gao, PhD, Institute of materia medica, Di AO Pharmaceutical Group, Chengdu 610041, People's Republic of China. Email: gxplww{at}hotmail.com, and Guolin Zhang, PhD, Chengdu Institute of Biology, the Chinese Academy of Sciences, Chengdu 610041, People's Republic of China. E-mail: zhanggl{at}cib.ac.cn

Abstract

Boehmeriasin A is a new phenanthroquinolizidine alkaloid recently isolated from the Boehmeria siamensis Craib (Urticaceae). In vitro biological activity assay demonstrated that this novel compound has wide-range, strong antitumor activity. This study is aimed to determine the effects of boehmeriasin A on breast cancer cell (MDA-MB-231 cell line). Proliferation assay and fluorescence activated cell sorter (FACS) showed that cell growth inhibition and G1 phase arrest of cell cycle were caused by boehmeriasin A. The concentrations resulting in total and 50% growth inhibition are 0.007 and 0.0035 μg/mL, respectively. Exposed in 0.007 μg/mL boehmeriasin A for 12 h, the G1 phase cell percent increased from 44.8% pre–drug treatment to 66.3%. Consistent with G1 arrest and cell growth inhibition, cyclin E2 and cyclin D1 messenger RNA expression in the cell was down-regulated with drug treatment. Then, few apoptotic cells were detected, and most other cells underwent differentiation, which is characterized by specific changes in cell morphology, lots of lipid droplet accumulation, and increasing expression of adipocyte differentiation–related protein. The result first demonstrates that boehmeriasin A potently inhibits the proliferation of breast cancer cell MDA-MB-231 via the G1 phase cell cycle arrest and differentiation induction, and as such, may be considered as candidate chemotherapeutic and/or chemopreventive agent for breast cancer.

  • boehmeriasin A
  • breast cancer cell
  • differentiation
  • G1 arrest

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