Molecular mechanism of solid tumor growth inhibition by a new differentiation inducer and molecular target agents

• Project/Area Number: 25462007
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: General surgery
• Research Institution: Shimane University (2014-2015); Research Institute for Clinical Oncology, Saitama Cancer Center (2013)
• Principal Investigator: KASUKABE TAKASHI 島根大学, 医学部, 特任教授 (50152658)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000); Fiscal Year 2015: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2014: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2013: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
• Keywords: コチレニンＡ / 三酸化ヒ素 / 分化誘導剤 / 乳癌細胞 / 増殖抑制 / 併用効果 / アポトーシス / 活性化酸素 / 癌 / 薬剤反応性 / シグナル伝達 / フェロトーシス / 発生・分化 / 薬剤反応

Outline of Final Research Achievements

We have examined whether a new differentiation inducer of leukemia cells can suppress the proliferation of solid tumor cells. In this study we found that cotylenin A significantly potentiate arsenic trioxide-induced inhibition of cell growth of human breast and pancreatic cancer cells. The combined treatment with cotylenin A and arsenic trioxide induced cleaved caspase-7 in human breast cancer MCF-7 cells at the concentration which arsenic trioxide alone scarcely induced and cotylenin A alone only weakly induced. Expression of survivin was markedly decreased with the presence of both cotylenin A and arsenic trioxide. The pretreatment with N-acetylcysteine significantly reduced the combination treatment-induced cell growth inhibition. These data suggest that induction of cleaved caspase-7, inhibition of survivin and oxidative responses are important events in the corporative inhibition in the growth of MCF-7 cells.

Research Products

• [Journal Article] Vitamin K2 and cotylenin A synergistically induce monocytic differentiation and growth arrest along the suppression of c-MYC expression and induction of cyclin G2 expression in human leukemia HL-60 cells. (2015)
  • Author(s): Maniwa, Y., Kasukabe, T., Kumakura, S.
  • Journal Title: Int. J. Oncol. Volume: 47 Issue: 2 Pages: 473-480
  • DOI: 10.3892/ijo.2015.3028
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Cotylenin A and arsenic trioxide cooperatively suppress cell proliferation and cell invasion activity in human breast cancer cells (2015)
  • Author(s): Kasukabe, T., Okabe-Kado, J., Kato, N., Honma, Y., Kumakura, S.
  • Journal Title: Int. J. Oncol. Volume: 46 Pages: 841-848
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Inhibition of rapamycin-induced Akt phosphorylation by cotylenin A correlates with their synergistic growth inhibition. (2013)
  • Author(s): Kasukabe T., Okabe-Kado J., Haranosono Y., Kato N., Honma Y.
  • Journal Title: International Journal of Oncology Volume: 42 Issue: 2 Pages: 765-775
  • DOI: 10.3892/ijo.2012.1745
• [Presentation] Cotylenin A and piperlongumine synergistically inhibit cell proliferation of several types of cancer cells. (2015)
  • Author(s): Kasukabe, T, Kado, J., Honma, Y.
  • Organizer: 第74回 日本癌学会学術総会
  • Place of Presentation: 名古屋（名古屋国際会議場）
  • Year and Date: 2015-10-09
• [Presentation] Effects of cotylenin A and phenethyl isothiocyanate on the formation of tumorshperes from human pancreatic tumor cells (2014)
  • Author(s): Kasukabe, T, Kado, J., Honma, Y
  • Organizer: 第73回 日本癌学会学術総会
  • Place of Presentation: 横浜、パシフィコ横浜
  • Year and Date: 2014-09-27
• [Presentation] 分化誘導剤コチレニンＡと植物由来イソチオシアネート(PEITC)のよる膵臓癌細胞の相乗的アポトーシス誘導
  • Author(s): 粕壁 隆、角 純子、本間良夫
  • Organizer: 日本癌学会
  • Place of Presentation: パシフィコ横浜
• [Remarks] http://www.shimane-u-education.jp