On the Sulfation and Methylation of Catecholestrogens in Human Mammary Epithelial Cells and Breast Cancer Cells(Miscellaneous)

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概要

• 論文の詳細を見る

• Prolonged exposure to high level of estrogen is a known risk factor for breast carcinogenesis. In cells, estrogens, in particular estrone (E_1) and 17β-estradiol (E_2), can be converted to catecholestrogens (CEs) which may be oxidized to form CE-semiquinones and CE-quinones that are capable of binding to DNA to induce mutations, followed by carcinogenesis. Whether the body is equipped with protective mechanisms against potentially harmful CEs, therefore, is an important issue. The present study was designed to examine the role of sulfation in the metabolism of CEs. MCF-7 breast cancer cells and MCF 10A human mammary epithelial cells were metabolically labeled with [^<35>S]sulfate in the presence of individual CEs. Analysis of the labeling media showed the generation and release of exclusively [^<35>S]sulfated 2-methoxy-E_1 or [^<35>S]sulfated 2- or 4-methoxy-E_2 by cells labeled in the presence of 2-OH-E_1 or 2- or 4-OH-E_2. Whereas both [^<35>S]sulfated 4-methoxy-E_1 and [^<35>S]sulfated 4-OH-E_1 were detected in the labeling media of cells labeled in the presence of 4-OH-E_1. These results indicated a concerted action of catechol-O-methyltransferase (COMT) and the cytosolic sulfotransferase (SULT) enzyme(s) in the metabolism of CEs. Enzymatic assays revealed that, five (SULT1A1, SULT1A2, SULT1A3, SULT1C4, and SULT1E1) of eleven known human SULTs tested could use CEs and methoxyestrogens (MEs) as substrates, with SULT1E1 displaying the strongest sulfating activity.

• 公益社団法人日本薬学会の論文
• 2008-04-01

著者

• 安田 伸

  東海大学農学部バイオサイエンス学科

• 安田 伸

  九州大学大学院農学研究院生物機能科学部門生物機能化学講座食糧化学教室

• YASUDA Shin

  Department of Pharmacology, College of Pharmacy, The University of Toledo

• LIU Ming-Cheh

  Department of Pharmacology, College of Pharmacy, The University of Toledo

• Yasuda Shin

  Tokai Univ. Kumamoto Jpn

• Liu M‐c

  Dep. Of Pharmacology Coll. Of Pharmacy The Univ. Of Toledo

• Yasuda Shin

  Department Of Pharmacology College Of Pharmacy The University Of Toledo

• Yasuda Shin

  School Of Agriculture Tokai University

• Yasuda Shin

  Department Of Bioscience School Of Agriculture Tokai University

• Liu Ming-Yih

  National Synchrotron Radiation Research Center, Taiwan

• HUI Ying

  Department of Pharmacology, College of Pharmacy, The University of Toledo

• WU Yi-yong

  Gynecology and Obstetric Department, Beijing Hospital

• Wu Yi-yong

  Gynecology And Obstetric Department Beijing Hospital

• Liu Ming-cheh

  Department Of Pharmacology College Of Pharmacy The University Of Toledo

• Hui Ying

  Department of Pharmacology, College of Pharmacy, The University of Toledo:Graduate School of Peking Union Medical College

• LIU Ming-Cheh

  Department of Biochemistry, The University of Texas Health Center at Tyler

• Liu Ming-Yih

  National Synchrotron Radiation Research Center

• 安田 伸

  東海大・農・バイオ

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