Development of a nobel strategy for chemoprevention of colorectal carcinogenesis by using newly synthesized organic compounds derived from natural dietary constituents
| Project/Area Number |
16590571
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Gastroenterology
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| Research Institution | TOHOKU UNIVERSITY |
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Principal Investigator |
SHIBATA Hiroyuki TOHOKU UNIVERSITY, HOSPITAL, LECTURER, 病院, 講師 (50260071)
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| Co-Investigator(Kenkyū-buntansha) |
IWABUCHI Yoshiharu TOHOKU UNIVERSITY, GRADUATE SCHOOL OF PHARMACEUTICAL SCIENCE, PROFESSOR, 大学院・薬学系研究科, 教授 (20211766)
加藤 誠之 東北大学, 大学病院, 助手 (60333887)
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| Project Period (FY) |
2004 – 2005
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| Project Status |
Completed (Fiscal Year 2005)
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| Budget Amount *help |
¥3,200,000 (Direct Cost: ¥3,200,000)
Fiscal Year 2005: ¥1,600,000 (Direct Cost: ¥1,600,000)
Fiscal Year 2004: ¥1,600,000 (Direct Cost: ¥1,600,000)
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| Keywords | beta-catenin / Ki-Ras / Cyclin-D1 / c-Myc / erbb2 / chemoprevention / phytochemical / β-catenin / Ki-ras / cyclin D1 / erbb2 / 家族性大腸腺腫症 / 化学発癌予防 |
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| Research Abstract |
Curcumin is a dietary constituent of turmeric that is widely used as a spice. Curcumin is a well-studied phytochemical that has a potential to suppress the growth of many cancer cell lines, while that has less toxicity as it is used for daily food. In this study, we have raised the goal to synthesize the new compounds from curcumin bearing the strengthen ability to suppress the growth of tumor cells, but keeping its less toxicity, and to establish a nobel strategy for medication of cancer treatment. The first cycle of the screening, we synthesized a new curcumin analog, GO-035 that have 4 times higher growth suppressive ability. Then we have synthesized over 50 compounds derived from GO-035. Finally two analogs termed GO-Y030 and GO-Y031 have been found out that have 40 times or more growth suppressive abilities against colorectal cancer cell lines. The common characteristic feature of these compounds is a pentanoid having the symmetrical addition of the alkoxy groups to the aromatic rings at both ends. These compounds have a stronger growth suppressive potential against a variety of cancer cell lines derived from stomach, colon, lung, pancreas, ovary, melanoma and so on, compared with chemotherapeutic agents such as cis-platine, 5-FU and irinotecan. The improvements of mechanical aspects of these compounds are the higher potentials to induce a G2/M phase arrest, apoptosis and down-regulation of various oncoproteins including beta-catenin, Ki-Ras, Cyclin-D1, c-Myc and erbb2 at much lower concentration than curcumin. On the other hands, there is no harmful effect on the primary hepatocytes at even 100 micromolar. There is no toxic effect on the mice fed with these conpounds (0.1% (w/w)in daily diet). These features of the compounds is thought to be ideal for not only chemotherapy but also chemoprevention.
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Report
(3 results)
Research Products
(3 results)
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[Patent(Industrial Property Rights)] 特許権2005
Inventor(s)
柴田浩行, 岩渕好治, 大堀久詔, 山越博幸, 角道祐一
Industrial Property Rights Holder
柴田浩行, 岩渕好治, 大堀久詔, 山越博幸, 角道祐一
Industrial Property Number
2005-187394
Filing Date
2005-06-27
Description
「研究成果報告書概要(和文)」より
Related Report
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