2023 Fiscal Year Annual Research Report
Investigation on naphthylisoquinoline alkaloids as potential antiausterity chemotherapy for pancreatic cancer
| Project/Area Number |
23H02104
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| Allocation Type | Single-year Grants |
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| Research Institution | University of Toyama |
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Principal Investigator |
Suresh Awale 富山大学, 学術研究部薬学・和漢系, 准教授 (00377243)
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| Co-Investigator(Kenkyū-buntansha) |
藤井 努 富山大学, 学術研究部医学系, 教授 (60566967)
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| Project Period (FY) |
2023-04-01 – 2028-03-31
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| Keywords | pancreatic cancer / antiausterity / napthylisoquinolines / antitumor agents / in vivo / chemical biology |
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| Outline of Annual Research Achievements |
We investigated naphthylisoquinoline alkaloids as a potential new chemotherapeutic agent against pancreatic cancer. In 2023, we screened over 200 naphthylisoquinoline alkaloids against MIA PaCa-2 pancreatic cancer cell line and identified promising candidates. Study on structure-activity relationship to guide future development has been achieved. We've also explored the molecular mechanisms of selected compounds, which could lead to a deeper understanding of their anti-cancer effects. In addition, we also discovered novel naphthoquinones as potent antiausterity agents against human PANC-1 pancreatic cancer cells and published the results. Our findings hold promise for the development of novel, targeted treatments for this aggressive disease.
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| Current Status of Research Progress |
Current Status of Research Progress
2: Research has progressed on the whole more than it was originally planned.
Reason
We've screened a vast library of NIQs, and identified several potent candidates with selective cytotoxicity against pancreatic cancer cells in nutrient-deprived conditions at nanomolar concentration range. We're now investigating the molecular mechanisms of these promising compounds.
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| Strategy for Future Research Activity |
We'll extensively study the effects of our active NIQ compounds on cancer cell morphology, migration, colony formation, and chemotaxis. We'll also investigate their ability to block survival pathways within the pancreatic tumor microenvironment, aiming to enhance cancer cell death. Finally, we'll evaluate the efficacy of selected NIQs against orthotopic MIA PaCa-2 tumors, both as single agents and in combination with gemcitabine (GEM).
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