Development of the analytical method for estrogen-o-quinones and its application to the study on the initiation mechanism of human breast cancer

• Project/Area Number: 22590041
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Physical pharmacy
• Research Institution: Tohoku Pharmaceutical University
• Principal Investigator: YAMASHITA Kouwa 東北薬科大学, 薬学部, 教授 (80382670)
• Co-Investigator(Kenkyū-buntansha): OHNO Ken-ichi 東北薬科大学, 薬学部, 講師 (20347272) ; KATO Hajime 東北薬科大学, 薬学部, 助教 (80584458) ; KOMATSU Sachiko 東北薬科大学, 薬学部, 助手 (00438566) ; 沼澤 光輝 東北薬科大学, 薬学部, 教授 (90006338)
• Project Period (FY): 2010 – 2012
• Project Status: Completed (Fiscal Year 2012)
• Budget Amount: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000); Fiscal Year 2012: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2011: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2010: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
• Keywords: 乳がん / エストロゲン / オルトキノン / フェナジン誘導体 / 質量分析 / 分析化学 / エストロゲンオルトキノン / 定量分析 / LC-MS / LC-ESI-MS/MS / ヘムタンパク

Research Abstract

Selective and sensitive analytical method for estrogen-o-quinones derived from catechol estrogen with enzymatic or non-enzymatic manner was developed based on the use of phenazine derivatization and LC-MS. The present method enabled to determine the catalytic activity of protein and some metal ions on the process of oxidation of catechol estrogens to the corresponding o-quinones. Furthermore, analytical method for the glutathione and L-cysteine conjugates of these o-quinones was established as one of the model for determining protein adducts of o-quinones.

Research Products

• [Journal Article] Structures and biomimetic synthesis of a Novel α-pyrone polyketide of an endophytic Penicillium sp (2013)
  • Author(s): T, Asai, D. Luo, K. Yamashita, Y. Oshima
  • Journal Title: Catharanthus roseus, Org. Lett Volume: 15 Issue: 5 Pages: 1021-1023
  • DOI: 10.1021/ol303506t
  • Peer Reviewed
• [Journal Article] Structures and Biomimetic Synthesis of Novel a-Pyrone Polyketide of an Endophytic Penicillium sp. Catharanthus roseus (2013)
  • Author(s): Teigo Asai, Dan Luo, kouwa Yamashita, Yoshiteru Oshima
  • Journal Title: Organic Letters Volume: 15 Pages: 1021-1023
  • Peer Reviewed
• [Journal Article] 18-Oxocortisol measurement in adrenal vein sampling as a biomarker for subclassifying primary aldosteroism (2011)
  • Author(s): Y. Nakamura, F. Satoh, R. Morimoto, M. Kudo, K. Takase, C E. Gometz-Sanchez, S. Honma, M. Okuyama, K. Yamashita, W E. Rainey, H. Sasano, S.Ito
  • Journal Title: J. Clin. Endcrinol. Metab Volume: 96 Issue: 8 Pages: E1272-E1278
  • DOI: 10.1210/jc.2010-2785
  • Peer Reviewed
• [Journal Article] Assay of labile estrogen o-quinones, a potent carcinogenic molecular species, by high performance liquid chromatographyelectrospray ionization mass spectrometry with phenazine derivatization (2010)
  • Author(s): K. Yamashita, A. Masuda, Y. Hoshino, S.Komatsu, M. Numazawa
  • Journal Title: J. Steroid Biochem. Mol. Biol Volume: 119 Pages: 141-148
• [Journal Article] Assay of labile estrogen-o-quinones, potent carcinogenic molecular species, by HPLC-electrosprayionization tandem mass spectrometry (2010)
  • Author(s): Kouwa Yamashita
  • Journal Title: J.Steroid Biochem.Mol.Biol. Volume: 119 Pages: 141-148
  • Peer Reviewed
• [Presentation] LC-ESI-MS/MS法による水酸化ステロイドのメタボローム解析(V)安定同位体標識カテコールエストロゲン-GSH 付加体の合成 (2013)
  • Author(s): 山下幸和、近藤恵美、白取未希、小松祥子、加藤創、大野賢一、沼澤光輝
  • Organizer: 日本薬学会第133 年会
  • Place of Presentation: 横浜
  • Year and Date: 2013-03-28
• [Presentation] LC-ESI-MS/MS法による水酸化ステロイドのメタボローム解析(V)安定同位体標識カテコールエストロゲン－GSH付加体の合成－ (2013)
  • Author(s): 山下幸和、近藤恵美、白取未希、小松祥子、加藤 創、大野賢一、沼澤光輝
  • Organizer: 日本薬学会第133年会
  • Place of Presentation: 横浜
• [Presentation] LC-ESI-MS/MS法による水酸化ステロイドのメタボローム解析(VI)－ステロイド硫酸抱合体の定量法の最適化－ (2013)
  • Author(s): 小松祥子、齋藤彩夏、榊 克教、山下幸和、沼澤光輝
  • Organizer: 日本薬学会第133年会
  • Place of Presentation: 横浜
• [Presentation] Pyridine-carboxylates as protonaffinitive derivatives in HPLC-ESI-MS/MS analysis of hydroxysteroids (2012)
  • Author(s): K. Yamashita, S. Komatsu, H. Kato, K.-I.Ohno
  • Organizer: 29^<th>LC/MS Montreux Symposium
  • Place of Presentation: Montreux
  • Year and Date: 2012-11-09
• [Presentation] LC-ESI-MS/MS によるアロマターゼ活性測定法の開発および従来法との比較 (2012)
  • Author(s): 小松祥子、鈴木直樹、高橋透、山下幸和、沼澤光輝
  • Organizer: 第51回日本薬学会東北支部大会
  • Place of Presentation: 青森
  • Year and Date: 2012-10-07
• [Presentation] Use of proton-affinitive derivatization in HPLC-ESI-MS analysis of biologically important carboxylic acids (2012)
  • Author(s): H. Kato, S. Mitsuzuka, K. Yamashita, M. Numazawa
  • Organizer: 19^<th>International Mass Spectrometry Conference
  • Place of Presentation: Kyoto
  • Year and Date: 2012-09-20
• [Presentation] LC-ESI-MS/MSによる水酸化ステロイドのメタボロム解析(IV)27 ステロイドの一斉分析 (2012)
  • Author(s): 山下幸和、小松祥子、加藤創、大野賢一、沼澤光輝、本間誠次郎
  • Organizer: 日本薬学会第132年会
  • Place of Presentation: 札幌
  • Year and Date: 2012-03-30
• [Presentation] LC-ESI-MS/MS法による水酸化ステロイドのメタボローム解析(IV)27ステロイドの一斉分析 (2012)
  • Author(s): 山下幸和、小松祥子、加藤創、大野賢一、沼澤光輝、本間誠次郎
  • Organizer: 日本薬学会第年会
  • Place of Presentation: 札幌(北海道大学)
  • Year and Date: 2012-03-30
• [Presentation] Use of proton-affinitive derivatization in HPLC-positive-ESI-MS analysis of biologically important carboxylic acids (2012)
  • Author(s): Hajime Kato, Shin Mitsuzuka, Kouwa Yamashita, Mitsuteru Numazawa
  • Organizer: 19th International Mass Spectrometry Conference
  • Place of Presentation: 京都
• [Presentation] LC-ESI-MS/MSによるアロマターゼ活性測定法の開発および従来法との比較 (2012)
  • Author(s): 小松祥子、鈴木直樹、高橋 透、山下幸和、沼澤光輝
  • Organizer: 第51回日本薬学会東北支部大会
  • Place of Presentation: 青森
• [Presentation] Pyridine-carboxylates as proton-affinitive derivatives in HPLC-ESI-MS/MS analysis of hydroxysteroids (2012)
  • Author(s): Kouwa Yamashita, Sachiko Komatsu, Hajime Katoh, Ken-ichi Ohno
  • Organizer: 29th LC/MS Montreux Symposium
  • Place of Presentation: Switzerland
• [Presentation] エストロゲンオルトキノンによるタンパク修飾(I)-L-Cys, N-Ac-L-Cys 及び GSH-共有結合体の調製とカテコール/キノン平衡 (2011)
  • Author(s): 白取未希、加藤創、山下幸和、沼澤光輝
  • Organizer: 第50回日本薬学会東北支部大会
  • Place of Presentation: 仙台
  • Year and Date: 2011-10-30
• [Presentation] An approach to the microdetermination of labile estrogen o-quinones by liquid chromatographyelectrospray ionization tandem mass spectrometry (2010)
  • Author(s): K. Yamashita, S. Komatsu, A. Masuda, M. Numazawa
  • Organizer: 58^<th>ASMS Confererence
  • Place of Presentation: Salt Lake City, USA
  • Year and Date: 2010-05-25
• [Presentation] An approach to the microdetermination of labile estrogen-o-quinones by liquid chromatography-electrospray ionization tandem mass spectrometry (2010)
  • Author(s): Kouwa Yamashita
  • Organizer: 58^<th> ASMS Conference on Mass Spectrometry and Allied Topics
  • Place of Presentation: Salt Lake City, Utah USA
  • Year and Date: 2010-05-24
• [Book] Testosterone: Biochemistry, Therapeutic Uses and Physiological Effects (2012)
  • Author(s): K. Yamashita (ed. by Konstantin Chichinadze)
  • Total Pages: 193
  • Publisher: Nova Scientific Publishers Inc
• [Book] Testosterone: Biochemistry, Therapeutic Uses and Physiological Effects (2012)
  • Author(s): Kouwa Yamashita (ed. by Konstantin Chichinadze)
  • Total Pages: 193
  • Publisher: Nova Scientific Publishers Inc
• [Remarks]
  • URL: http://www.tohoku-pharm.ac.jp/laboratory/rinsyob/index.html
• [Remarks] 東北薬科大学臨床分析化学教室ホームページ（教育研究組織）
  • URL: http://www.tohoku-pharm.ac.jp/laboratory/rinsyob/index.html
• [Remarks]
  • URL: http://www.tohoku-pharm.ac.jp/laboratory/rinsyob/ronbun.html
• [Remarks]
  • URL: http://www.tohoku-pharm.ac.jp/laboratory/rinsyob/index.html