2022 Fiscal Year Final Research Report
Determination of Common Targets of Metal Complexes that Induce Programmed Cell Death of Cancer Cells and Development of New Anticancer Drugs
| Project/Area Number |
20K05712
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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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| Review Section |
Basic Section 37010:Bio-related chemistry
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| Research Institution | Tokyo University of Science |
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Principal Investigator |
Aoki Shin 東京理科大学, 薬学部生命創薬科学科, 教授 (00222472)
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| Project Period (FY) |
2020-04-01 – 2023-03-31
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| Keywords | イリジウム錯体－ペプチドハイブリッド / プログロム細胞死 / パラトーシス / 発光 / 小胞体 / ミトコンドリア / カルシウム |
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| Outline of Final Research Achievements |
We previously reported on that a cyclometalated iridium (Ir) complex-peptide hybrid (IPH) functionalized with a cationic KKKGG peptide unit on the 2-phenylpyridine ligand of Ir complex induces paraptosis, a relatively newly found programmed cell death (PCD), in cancer cells via the direct transport of calcium (Ca2+) from the endoplasmic reticulum (ER) to mitochondria. The results in this work suggest that the induction of paraptosis by IPH is associated with membrane fusion between mitochondria and the ER, subsequent Ca2+ influx from the ER to mitochondria, and the decrease in mitochondrial membrane potential. On the other hand, celastrol, a naturally-occurring triterpenoid, induces paraptosis, while not via ER-mitochondria membrane fusion. We conclude that the paraptosis induced by IPH (referred to as paraptosis II) proceeds via different signaling pathway from that of the previously-known paraptosis induced by celastrol (referred to as paraptosis I).
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| Free Research Field |
生物有機化学・生物無機化学
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| Academic Significance and Societal Importance of the Research Achievements |
プログラム細胞死（PCD）は、組織や器官の形成などに重要な役割を果たしており、代表的なPCDであるapoptosisの他、necroptosis、paraptosis、autophagyなどが報告されている。現在、がん細胞のapoptosisを誘導する抗がん剤が使われているが、耐性が生じ抗がん作用が減弱するなどの問題があるため、異なるPCDの誘起薬剤の開発が求められている。本研究は、従来報告されていたparaptosis (paraptosis I)に類似しているものの、異なるメカニズムで進行するparaptosis (paraptosis II)を発見し、新規抗がん剤設計の指針を示した。
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