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Investigation on naphthylisoquinoline alkaloids as potential antiausterity chemotherapy for pancreatic cancer

Research Project

Project/Area Number 23K26797
Project/Area Number (Other) 23H02104 (2023)
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeMulti-year Fund (2024)
Single-year Grants (2023)
Section一般
Review Section Basic Section 37030:Chemical biology-related
Research InstitutionUniversity of Toyama

Principal Investigator

Suresh Awale  富山大学, 学術研究部薬学・和漢系, 准教授 (00377243)

Co-Investigator(Kenkyū-buntansha) 藤井 努  富山大学, 学術研究部医学系, 教授 (60566967)
Project Period (FY) 2023-04-01 – 2028-03-31
Project Status Granted (Fiscal Year 2024)
Budget Amount *help
¥18,590,000 (Direct Cost: ¥14,300,000、Indirect Cost: ¥4,290,000)
Fiscal Year 2027: ¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000)
Fiscal Year 2026: ¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000)
Fiscal Year 2025: ¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000)
Fiscal Year 2024: ¥3,510,000 (Direct Cost: ¥2,700,000、Indirect Cost: ¥810,000)
Fiscal Year 2023: ¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000)
KeywordsPancreatic cancer / antiausterity / napthylisoquinolines / antitumor agents / in vivo / pancreatic cancer / chemical biology / Pancreatic canecer / anti tumor agents
Outline of Research at the Start

This project aimed to investigate naphthylisoquinoline alkaloids as new anti-tumor chemotherapeutic agents and provide strong preclinical evidence for drug development against pancreatic cancer through in vivo xenograft tests.

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.

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.

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).

Report

(1 results)
  • 2023 Annual Research Report
  • Research Products

    (7 results)

All 2024 2023

All Journal Article (4 results) (of which Int'l Joint Research: 4 results,  Peer Reviewed: 4 results,  Open Access: 1 results) Presentation (3 results) (of which Invited: 1 results)

  • [Journal Article] Droserone and dioncoquinone B, and related naphthoquinones as potent antiausterity agents against human PANC-1 pancreatic cancer cells2024

    • Author(s)
      Juthamart Maneenet, Nasir Tajuddeen, Hung Hong Nguyen, Rintaro Fujii, Blaise Kimbadi Lombe, Doris Feineis, Suresh Awale, Gerhard Bringmann
    • Journal Title

      Results in Chemistry

      Volume: 7 Pages: 101352-101352

    • DOI

      10.1016/j.rechem.2024.101352

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Justicidin B and related lignans from two South African Monsonia species with potent activity against HeLa cervical cancer cells2024

    • Author(s)
      Nasir Tajuddeen, Severin Muyisa, Juthamart Maneenet, Hung Hong Nguyen, Dashnie Naidoo-Maharaj, Vinesh Maharaj, Suresh Awale, Gerhard Bringmann
    • Journal Title

      Phytochemistry Letters

      Volume: 60 Pages: 234-238

    • DOI

      10.1016/j.phytol.2023.09.007

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Ugi Adducts as Novel Anti-austerity Agents against PANC-1 Human Pancreatic Cancer Cell Line: A Rapid Synthetic Approach2023

    • Author(s)
      Keisuke Tomohara*, Juthamart Maneene, Nao Ohashi, Takeru Nose, Rintaro Fujii, Min Jo Kim, Sijia Sun, Suresh Awale*
    • Journal Title

      Biological and Pharmaceutical Bulletin

      Volume: 46 Issue: 10 Pages: 1412-1420

    • DOI

      10.1248/bpb.b23-00224

    • ISSN
      0918-6158, 1347-5215
    • Year and Date
      2023-10-01
    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Piper longum Constituents Induce PANC-1 Human Pancreatic Cancer Cell Death under Nutrition Starvation2023

    • Author(s)
      Yuki Fujihashi, Min Jo Kim, Juthamart Maneenet, Suresh Awale
    • Journal Title

      Chemistry & Biodiversity

      Volume: 20 Issue: 9

    • DOI

      10.1002/cbdv.202300280

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Presentation] How to Find a Cure for Pancreatic Cancer? Strategies and Leads from Natural Products2024

    • Author(s)
      Suresh Awale
    • Organizer
      Faculty of Pharmaceutical Science, Khon Kaen University, Thailand
    • Related Report
      2023 Annual Research Report
    • Invited
  • [Presentation] Nicolaioidesin C: A Promising Antiausterity Agent with Antitumor Efficacy in a Pancreatic Cancer Xenograft Model2024

    • Author(s)
      Suresh Awale, Juthamart Maneenet, Nguyen Duy Phan, Tsutomu Fujii, Takuya Okada, Naoki Toyooka
    • Organizer
      日本薬学会第144年会
    • Related Report
      2023 Annual Research Report
  • [Presentation] Meroterpenoids from Callistemon subulatus induce PANC-1 human pancreatic cancer cell death by targeting the Akt/mTOR/Autophagy pathway2023

    • Author(s)
      Juthamart Maneenet,Rintaro Fujii,Hung Hong Nguyen,Suresh Awale
    • Organizer
      日本生薬学会第70回年会
    • Related Report
      2023 Annual Research Report

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Published: 2023-04-18   Modified: 2024-12-25  

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