Asian Pacific Journal of Cancer Prevention

  • 제15권1호
  • /
  • Pages.495-499
  • /
  • 2014
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  • 1513-7368(pISSN)
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  • 2476-762X(eISSN)
아시아태평양암예방학회 (Asian Pacific Journal of Cancer Prevention)
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Preferential Induction of CYP1A1 over CYP1B1 in Human Breast Cancer MCF-7 Cells after Exposure to Berberine

  • Wen, Chun-Jie (Institute of Life Sciences, Chongqing Medical University) ;
  • Wu, Lan-Xiang (Institute of Life Sciences, Chongqing Medical University) ;
  • Fu, Li-Juan (Institute of Life Sciences, Chongqing Medical University) ;
  • Shen, Dong-Ya (Institute of Life Sciences, Chongqing Medical University) ;
  • Zhang, Xue (Institute of Life Sciences, Chongqing Medical University) ;
  • Zhang, Yi-Wen (Institute of Clinical Pharmacology, Central South University) ;
  • Yu, Jing (Institute of Clinical Pharmacology, Central South University) ;
  • Zhou, Hong-Hao (Institute of Life Sciences, Chongqing Medical University)
  • 발행 : 2014.01.15
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초록

Estrogens are considered the major breast cancer risk factor, and the carcinogenic potential of estrogens might be attributed to DNA modification caused by derivatives formed during metabolism. $17{\beta}$-estradiol ($E_2$), the main steroidal estrogen present in women, is metabolized via two major pathways: formation of 2-hydroxyestradiol (2-OH $E_2$) and 4-hydroxyestradiol ($4-OH\;E_2$) through the action of cytochrome P450 (CYP) 1A1 and 1B1, respectively. Previous reports suggested that $2-OH\;E_2$ has putative protective effects, while $4-OH\;E_2$ is genotoxic and has potent carcinogenic activity. Thus, the ratio of $2-OH\;E_2/4-OH\;E_2$ is a critical determinant of the toxicity of $E_2$ in mammary cells. In the present study, we investigated the effects of berberine on the expression profile of the estrogen metabolizing enzymes CYP1A1 and CYP1B1 in breast cancer MCF-7 cells. Berberine treatment produced significant induction of both forms at the level of mRNA expression, but with increased doses produced 16~ to 52~fold greater induction of CYP1A1 mRNA over CYP1B1 mRNA. Furthermore, berberine dramatically increased CYP1A1 protein levels but did not influence CYP1B1 protein levels in MCF-7 cells. In conclusion, we present the first report to show that berberine may provide protection against breast cancer by altering the ratio of CYP1A1/CYP1B1, could redirect $E_2$ metabolism in a more protective pathway in breast cancer MCF-7 cells.

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