Relationship between anthracycline anticancer drug and reactive oxygen species; reconstruction of information for its elucidation
| Project/Area Number |
16K08420
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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 |
Medical pharmacy
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| Research Institution | Kinjo Gakuin University |
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Principal Investigator |
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| Project Period (FY) |
2016-04-01 – 2020-03-31
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| Project Status |
Completed (Fiscal Year 2019)
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| Budget Amount *help |
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2018: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2017: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2016: ¥2,990,000 (Direct Cost: ¥2,300,000、Indirect Cost: ¥690,000)
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| Keywords | アントラサイクリン / 抗がん剤 / 活性酸素 / DNA損傷 / アポトーシス / アクラルビシン / doxorubicin / ROS / PARP / 薬学 / 癌 / 薬理学 / シグナル伝達 |
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| Outline of Final Research Achievements |
We reconstructed the relational information between anthracycline anticancer drug (AC) and reactive oxygen species (ROS). Experiments were evaluated for DNA damage and cell death in doxorubicin (DOX), epirubicin (EPI), daunorubicin (DNR), idarubicin (IDR), aclarubicin (ACL). AC damaged DNA in the presence of Cu (II), and its intensity was (DOX, EPI) > (THP, IDR) > ACR >> DNR, and no damage was observed in DNR. On the other hand, as a result of detailed examination of cell death of THP, ACR and IDR, it was suggested that ROS was involved in cell death of THP and ACR, but ROS was not involved in IDR. In addition, Cu (I) was involved in ACR cell death, and the importance of Cu was clarified.
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| Academic Significance and Societal Importance of the Research Achievements |
アントラサイクリン系抗がん剤の作用機序として活性酸素種の関与が知られているが、その詳細については明らかでない。我々はこれまでドキソルビシンのCu(II) 存在下での新しい酸化的DNA損傷機構を明らかにしたが、今回、ピラルビシン、アクラルビシン、イダルビシンでも同様にCu(II)存在下でDNA損傷することを明らかにし、アクラルビシンによる細胞死でCu(I)の関与を明らかにした。これらの成果はアントラサイクリンの新しい作用機序の解明につながり、創薬の場、臨床の場へフィードバックすることにより、新規抗がん剤の開発、がんの薬物治療の進展につながり、社会への還元が期待される。
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Report
(5 results)
Research Products
(18 results)
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[Journal Article] Oxidative DNA damage and apoptosis induced by aclarubicin, an anthracycline: role of hydrogen peroxide and copper.2019
Author(s)
Mizutani H, Hayashi Y, Hashimoto M, Imai M, Ichimaru Y, Kitamura Y, Ikemura K, Miyazawa D, Ohta K, Ikeda Y, Maeda T, Yoshikawa M, Hiraku Y, Kawanishi S
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Journal Title
Anticancer Res
Volume: 39
Issue: 7
Pages: 3443-3451
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Oxidative DNA damage induced by pirarubicin, an anthracycline anticancer agent, in the presence of copper(II).2018
Author(s)
Mizutani H, Nishimoto A, Hotta S, Ikemura K, Imai M, Miyazawa D, Ohta K, Ikeda Y, Maeda T, Yoshikawa M, Hiraku Y, Kawanishi S
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Journal Title
Anticancer Research
Volume: 38
Issue: 5
Pages: 2643-2648
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Pirarubicin, an anthracycline anticancer agent, induces apoptosis through generation of hydrogen peroxide.2017
Author(s)
H. Mizutani, S. Hotta, A. Nishimoto, K. Ikemura, D. Miyazawa, Y. Ikeda, T. Maeda, M. Yoshikawa, Y. Hiraku, S. Kawanishi
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Journal Title
Anticancer Res.
Volume: 37
Pages: 6063-6069
Related Report
Peer Reviewed / Open Access
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