Basic research for development of cancer prevention by inhibitory effect of food constituents on the signal transduction pathways associated with carcinogenesis

• Project/Area Number: 23790669
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Hygiene
• Research Institution: Kyoto Prefectural University of Medicine
• Principal Investigator: YOGOSAWA Shingo 京都府立医科大学, 医学研究科, 助教 (70381936)
• Project Period (FY): 2011 – 2012
• Project Status: Completed (Fiscal Year 2012)
• Budget Amount: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000); Fiscal Year 2012: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000); Fiscal Year 2011: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
• Keywords: 予防医学 / 食品成分 / 癌予防 / 細胞増殖シグナル伝達系 / 細胞周期 / シグナル伝達経路 / MEK-ERK経路 / PI3K-AKT経路 / CDK阻害因子

Research Abstract

MEK-ERK or PI3K-Akt signal transduction pathways are accelerated in many cancers and considered to be the very important molecular targets not only for the cancer therapy but also for the cancer prevention. To develop a novel strategy for cancer prevention targeting the major signal transduction pathways associated with carcinogenesis by food constituents, growth inhibitory effect of brassinin ordehydrozingerone on human colon cancer cells was studied and the molecular mechanisms were analyzed. Brassinin, derived from cruciferous vegetables like cabbage or broccoli, repressed the growth of human colon cancer HT -29 cells mediated by inhibition of PI3K-Akt pathway . Dehydrozingerone, derived from a ginger, and is known as a structural half analogue of curcumin, which is known to inhibit MEK-ERK pathway. Dehydrozingerone repressed the growth of HT -29 cells in association with accumulation of intracellular reactive oxygen species (ROS). In addition, combination of a PI3K inhibitor with histone deacetylase inhibitor was shown to be useful for growth inhibition of human endometrial carcinoma HEC-1A cells.

Research Products

• [Journal Article] Dehydrozingerone, a structural analogue of curcumin, induces cell-cycle arrest at the G2/M phase and accumulates intracellular ROS in HT -29 human colon cancer cells (2013)
  • Author(s): Yogosawa S, Yamada Y, Yasuda S, Sun Q, Takizawa K, Sakai T
  • Journal Title: J Nat Prod Volume: Vol. 75、 No. 12 Issue: 12 Pages: 2088-2093
  • DOI: 10.1021/np300465f
  • Peer Reviewed
• [Journal Article] Combination of a novel HDAC inhibitor OBP-801/YM753 and a PI3K inhibitor LY294002 synergistically induces apoptosis in human endometrial carcinoma cells due to increase of Bim with accumulation of ROS (2013)
  • Author(s): Yoshioka T, Yogosawa S, Yamada T, Kitawaki J, Sakai T.
  • Journal Title: Gynecologic Oncology Volume: 129 Issue: 2 Pages: 425-432
  • DOI: 10.1016/j.ygyno.2013.02.008
  • Peer Reviewed
• [Journal Article] Brassinin induces G1 phase arrest through increase of p21 and p27 by inhibition of the phosphatidylinositol 3-kinase signaling pathway in human colon cancer cells (2012)
  • Author(s): Izutani Y, Yogosawa S, Sowa Y, Sakai T
  • Journal Title: Int J Oncol Volume: Vol. 40、 No. 3 Pages: 816-824
  • DOI: 10.3892/ijo.2011.1246
  • Peer Reviewed
• [Journal Article] p53 inactivation upregulates p73 expression through E2F-1 mediated transcription (2012)
  • Author(s): Tophkhane C, Yang SH, Jiang Y, Ma Z,Subramaniam D, Anant S, Yogosawa S, Sakai T, Liu WG, Edgerton S, Thor A, Yang X
  • Journal Title: PLoS One Volume: 7 Issue: 8 Pages: e43564-e43564
  • DOI: 10.1371/journal.pone.0043564
  • Peer Reviewed
• [Presentation] ヒト大腸癌細胞におけるブラシニンのPI3K-Akt 経路を介する細胞周期停止誘導効果 (2012)
  • Author(s): 与五沢真吾、泉谷泰行、曽和義広、酒井敏行
  • Organizer: 第19回日本がん予防学会
  • Place of Presentation: じゅうろくプラザ(岐阜市文化産業交流センター)
  • Year and Date: 2012-06-23
• [Presentation] ショウガ由来成分デヒドロジンゲロンは ROS 依存的に細胞増殖を抑制する (2012)
  • Author(s): 与五沢真吾、山田恭正、孫〓、安田周祐、瀧澤香織、曽和義広、酒井敏行
  • Organizer: 第82回日本衛生学会学術総会
  • Place of Presentation: 京都大学
  • Year and Date: 2012-03-25
• [Presentation] デヒドロジンゲロンのアナログによるヒト大腸がん細胞増殖抑制効果 (2012)
  • Author(s): 山田恭正、与五沢真吾、孫〓、玉木友梨、酒井敏行
  • Organizer: 日本農芸化学会 2012 年度大会
  • Place of Presentation: 京都女子大学
  • Year and Date: 2012-03-24
• [Presentation] ショウガ由来成分デヒドロジンゲロンによる細胞増殖抑制効果 (2012)
  • Author(s): 与五沢真吾、山田恭正、安田周祐、瀧澤香織、孫〓、曽和義広、酒井敏行
  • Organizer: 第11回分子予防環境医学研究会
  • Place of Presentation: 倉敷市民会館
  • Year and Date: 2012-01-28
• [Presentation] デヒドロジンゲロンのアナログによるヒト大腸がん細胞増殖抑制効果 (2012)
  • Author(s): 山田恭正、与五沢真吾、孫琦、玉木友梨、酒井敏行
  • Organizer: 日本農芸化学会2012年度大会
  • Place of Presentation: 京都女子大学
• [Presentation] ショウガ由来成分デヒドロジンゲロンはROS依存的に細胞増殖を抑制する (2012)
  • Author(s): 与五沢真吾、山田恭正、孫琦、安田周祐、瀧澤香織、曽和義広、酒井敏行
  • Organizer: 第82回日本衛生学会学術総会
  • Place of Presentation: 京都大学
• [Presentation] Brassinin induces G1 phase arrest through increase of p21 and p27 by inhibition of PI3K/Akt signaling pathway (2011)
  • Author(s): 与五沢真吾、泉谷泰行、曽和義広、酒井敏行
  • Organizer: 第70回日本癌学会学術総会
  • Place of Presentation: 名古屋国際会議場
  • Year and Date: 2011-10-05
• [Presentation] インドール-3-カルビノールとガランギンの併用による細胞死増強 (2011)
  • Author(s): 与五沢真吾、瀧澤香織、孫〓、曽和義広、酒井敏行
  • Organizer: がん予防大会 2011 京都
  • Place of Presentation: 京都府立医科大学
  • Year and Date: 2011-06-21
• [Presentation] インドール-3-カルビノールとガランギンの併用による細胞死増強 (2011)
  • Author(s): 与五沢真吾、瀧澤香織、孫琦、曽和義広、酒井敏行
  • Organizer: がん予防大会2011京都
  • Place of Presentation: 京都府立医科大学
• [Presentation] Brassinin induces G1 phase arrest through increase of p21 and p27 by inhibition of PI3K/Akt signaling pathway. (2011)
  • Author(s): 与五沢真吾、泉谷泰行、曽和義広、酒井敏行
  • Organizer: 第70回日本癌学会学術総会
  • Place of Presentation: 名古屋国際会議場
• [Presentation] ヒト大腸癌細胞におけるブラシニンのPI3K-Akt 経路を介する細胞周期停止誘導効果
  • Author(s): 与五沢真吾、泉谷泰行、曽和義広、酒井敏行
  • Organizer: 第19回日本がん予防学会
  • Place of Presentation: じゅうろくプラザ（岐阜市文化産業交流センター）
• [Remarks]
  • URL: http://www.f.kpu-m.ac.jp/k/pubmed/