Screening of the novel target for cancer therapy based on the mechanisms of natural compounds

• Project/Area Number: 15K18821
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Applied molecular and cellular biology
• Research Institution: National Cardiovascular Center Research Institute (2017); Kyushu University (2015-2016)
• Principal Investigator: Kumazoe Motofumi 国立研究開発法人国立循環器病研究センター, 研究所, 特任研究員 (70737212)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000); Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2016: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000); Fiscal Year 2015: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
• Keywords: cGMP / Caner / EGCG / PDE3 / FOXO3 / がん / 天然物 / がん幹細胞 / 67LR / ケミカルバイオロジー / 抗がん作用

Outline of Final Research Achievements

Green tea polyphenol Epigallocatechin-3-O-gallate has anti-cancer effect. Several clinical trials show its anti-cancer effect, however, little is known its mechanisms. We previously reported that cGMP mediates anti-cancer effect of EGCG.Because EGCG also have strong suppressing effect on cancer stem cell properties, we hypothesized that cGMP itself has strong inhibitory effect on cancer stem cell properties. Our data shows some kind of cGMP inducer shows strong inhibitory effect on cancer stem cell properties.

Research Products

• [Journal Article] PDE3 inhibitor and EGCG combination treatment suppress cancer stem cell properties in pancreatic ductal adenocarcinoma (2017)
  • Author(s): Kumazoe M. et al
  • Journal Title: Scientific Reports Volume: -
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] FOXO3 is essential for CD44 expression in pancreatic cancer cells (2016)
  • Author(s): Kumazoe M. et al
  • Journal Title: Oncogene Volume: -
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Anti-cancer effect of EGCG and its mechanisms. (2016)
  • Author(s): Kumazoe M., Tachibana T.
  • Journal Title: Functional Foods in Health & Disease Volume: 6
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Metabolic Profiling-based Data-mining for an Effective Chemical Combination to Induce Apoptosis of Cancer Cells. (2015)
  • Author(s): Kumazoe M, Fujimura Y, Hidaka S, Kim Y, Murayama K, Takai M, Huang Y, Yamashita S, Murata M, Miura D, Wariishi H, Maeda-Yamamoto M, Tachibana H.
  • Journal Title: Sci Rep. Volume: 31 Issue: 1 Pages: 9474-9474
  • DOI: 10.1038/srep09474
  • Peer Reviewed / Open Access
• [Journal Article] Green tea polyphenol epigallocatechin-O-gallate induces cell death by acid sphingomyelinase activation in chronic myeloid leukemia cells. (2015)
  • Author(s): Huang Y., Kumazoe M. et. al.(equal contribution)
  • Journal Title: Oncology Reports Volume: 34 Issue: 3 Pages: 1162-1168
  • DOI: 10.3892/or.2015.4086
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Vardenafil, a clinically available phosphodiesterase inhibitor, potentiates the killing effect of EGCG on CLL cells. (2014)
  • Author(s): Kumazoe, M., Tsukamoto, S., Lesnick, C., Kay, N. E. Yamada, K., Shanafelt T. D. and Tachibana, H.
  • Journal Title: Br. J. Haematol. Volume: 168 Issue: 4 Pages: 610-613
  • DOI: 10.1111/bjh.13135
  • Peer Reviewed / Open Access / Acknowledgement Compliant