Cycloplatinated (II) Complex Based on Isoquinoline Alkaloid Elicits Ferritinophagy-Dependent Ferroptosis in Triple-Negative Breast Cancer Cells
The development and optimization of metal-based anticancer drugs with novel cytotoxic mechanisms have emerged as key strategies to overcome chemotherapeutic resistance and side effects. Agents that simultaneously induce ferroptosis and autophagic death have received extensive attention as potential modalities for cancer therapy. However, only a limited set of drugs or treatment modalities can synergistically induce ferroptosis and autophagic tumor cell death. In this work, we designed and synthesized four new cycloplatinated (II) complexes harboring an isoquinoline alkaloid C∧N ligand. On screening the in vitro activity of these agents, we found that Pt-3 exhibited greater selectivity of cytotoxicity, decreased resistance factors, and improved anticancer activity compared to cisplatin. Furthermore, Pt-3, which we demonstrate can initiate potent ferritinophagy-dependent ferroptosis, exhibits less toxic and better therapeutic activity than cisplatin in vivo. Our results identify Pt-3 as a promising candidate or paradigm for further drug development in cancer treatment.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2024 |
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| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:67 |
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| Enthalten in: |
Journal of medicinal chemistry - 67(2024), 8 vom: 25. Apr., Seite 6738-6748 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Wang, Feng-Yang [VerfasserIn] |
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| Links: |
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| Themen: |
9007-73-2 |
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| Anmerkungen: |
Date Completed 25.04.2024 Date Revised 25.04.2024 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1021/acs.jmedchem.4c00285 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM370159861 |
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| 500 | |a Date Revised 25.04.2024 | ||
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| 500 | |a Citation Status MEDLINE | ||
| 520 | |a The development and optimization of metal-based anticancer drugs with novel cytotoxic mechanisms have emerged as key strategies to overcome chemotherapeutic resistance and side effects. Agents that simultaneously induce ferroptosis and autophagic death have received extensive attention as potential modalities for cancer therapy. However, only a limited set of drugs or treatment modalities can synergistically induce ferroptosis and autophagic tumor cell death. In this work, we designed and synthesized four new cycloplatinated (II) complexes harboring an isoquinoline alkaloid C∧N ligand. On screening the in vitro activity of these agents, we found that Pt-3 exhibited greater selectivity of cytotoxicity, decreased resistance factors, and improved anticancer activity compared to cisplatin. Furthermore, Pt-3, which we demonstrate can initiate potent ferritinophagy-dependent ferroptosis, exhibits less toxic and better therapeutic activity than cisplatin in vivo. Our results identify Pt-3 as a promising candidate or paradigm for further drug development in cancer treatment | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 7 | |a Isoquinolines |2 NLM | |
| 650 | 7 | |a Antineoplastic Agents |2 NLM | |
| 650 | 7 | |a Ferritins |2 NLM | |
| 650 | 7 | |a 9007-73-2 |2 NLM | |
| 650 | 7 | |a Coordination Complexes |2 NLM | |
| 650 | 7 | |a Alkaloids |2 NLM | |
| 650 | 7 | |a isoquinoline |2 NLM | |
| 650 | 7 | |a JGX76Y85M6 |2 NLM | |
| 700 | 1 | |a Yang, Liang-Mei |e verfasserin |4 aut | |
| 700 | 1 | |a Wang, Shan-Shan |e verfasserin |4 aut | |
| 700 | 1 | |a Lu, Hui |e verfasserin |4 aut | |
| 700 | 1 | |a Wang, Xu-Sheng |e verfasserin |4 aut | |
| 700 | 1 | |a Lu, Yuan |e verfasserin |4 aut | |
| 700 | 1 | |a Ni, Wen-Xiu |e verfasserin |4 aut | |
| 700 | 1 | |a Liang, Hong |e verfasserin |4 aut | |
| 700 | 1 | |a Huang, Ke-Bin |e verfasserin |4 aut | |
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