Novel therapeutic and preventive strategy of resveratrol treatment in triple negative breast cancer cells
| Project/Area Number |
17K10561
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
General surgery
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| Research Institution | Jichi Medical University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
谷本 圭司 広島大学, 原爆放射線医科学研究所, 助教 (90335688)
林 慎一 東北大学, 医学系研究科, 教授 (60144862)
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| Project Period (FY) |
2017-04-01 – 2020-03-31
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| Project Status |
Completed (Fiscal Year 2019)
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| Budget Amount *help |
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2019: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2018: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2017: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
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| Keywords | トリプルネガティブ乳がん / レスベラトロール / 細胞形態 / 細胞浸潤能 / Bcl2阻害剤 / E-カドヘリン / p21 / ヒストンアセチル化 / DNAメチル化 / ヒストン修飾 / エピゲノム / エストロゲンレセプター / 分化誘導 / 癌 / 食品 / 生理活性 / 遺伝子 / 発現制御 |
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| Outline of Final Research Achievements |
Triple negative breast cancer (TNBC), that defined by lacking of ER and PR expression and HER2 amplification, shows aggressive phenotype, although no specific therapy has been established, except for hereditary breast cancer. Therefore, a novel therapeutic strategy for TNBC is strongly desired. We thus investigated the anticancer effects of resveratrol (RSV), one of the grape-derived polyphenols, on TNBC cells. RSV induced epithelial-like morphological changes, suppressed invasion capacity, and increased cytotoxicity of Bcl2 inhibitor (ABT263) in MDA-MB-231 and BT549-Luc cells. It also increased expression and histone acetylation of CDH1 and CDKN1A tumor suppressive genes. Moreover, transfection of CDKN1A siRNA reduced ABT263-induced apoptosis in RSV-treated MDA-MB-231 cells. In conclusion, this study demonstrated a potential of RSV as a novel therapeutic and preventive agent for TNBC through increased cytotoxicity of ABT263 and inhibition of metastatic capacity of TNBC cells.
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| Academic Significance and Societal Importance of the Research Achievements |
TNBCは悪性度が高く予後不良であることから、新規治療・予防法の開発が望まれている。本研究では、複数のTNBC細胞を用い、エピゲノム制御作用があるRSVの治療・予防薬としての有用性とその分子機構を示すことができた。食品成分であるRSVと他の薬剤との併用効果や、RSV単剤での転移能抑制作用が解明されたことは、新規エピゲノム治療薬として食品成分の可能性を示すという学術的意義に加え、特異的治療法が確立していない疾患に対する新規治療戦略としての社会的意義が大きいと考えられる。
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Report
(4 results)
Research Products
(6 results)
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[Journal Article] GLIS1, a novel hypoxia-inducible transcription factor, promotes breast cancer cell motility via activation of WNT5A.2020
Author(s)
Kazumi Shimamoto, Keiji Tanimoto*, Takahiro Fukazawa, Hideaki Nakamura, Akinori Kanai, Hidemasa Bono, Hiromasa Ono, Hidetaka Eguchi, Nobuyuki Hirohashi
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Journal Title
Carcinogenesis
Volume: inpress
Issue: 9
Pages: 1184-1194
DOI
Related Report
Peer Reviewed
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