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Apoptosis

, Volume 13, Issue 6, pp 748–755 | Cite as

A novel diquinolonium displays preclinical anti-cancer activity and induces caspase-independent cell death

  • Rose Hurren
  • Reza Beheshti Zavareh
  • Shadi Dalili
  • Tabitha Wood
  • David Rose
  • Hong Chang
  • Nazir Jamal
  • Hans Messner
  • Robert A. Batey
  • Aaron D. SchimmerEmail author
Original Paper

Abstract

Quinolines are a class of chemical compounds with emerging anti-cancer properties. Here, we tested the activity of series of quinolines and quinoline-like molecules for anti-cancer activity and identified a novel diquinoline, 1-methyl-2-[3-(1-methyl-1,2-dihydroquinolin-2-yliden)prop-1-enyl]quinolinium iodide (Q2). Q2 induced cell death in leukemia, myeloma, and solid tumor cell lines with LD50s in the low to submicromolar range. Moreover, Q2 induced cell death in primary acute myeloid leukemia (AML) cells preferentially over normal hematopoietic cells. In a mouse model of leukemia, Q2 delayed tumor growth. Mechanistically, Q2 induced cell death through caspase independent mechanisms. By electron microscopy, Q2 increased cytoplasmic vacuolization and mitochondrial swelling. Potentially consistent with the induction of autophagic cell death, Q2 treatment led to a punctate distribution of LC3 and increased MDC staining. Thus, Q2 is a novel quinolinium with preclinical activity in malignancies such as leukemia and myeloma and warrants further investigation.

Keywords

Caspase-independent cell death Preclinical activity Leukemia Myeloma Quinoline 

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Copyright information

© Springer Science+Business Media, LLC 2008

Authors and Affiliations

  • Rose Hurren
    • 1
  • Reza Beheshti Zavareh
    • 1
    • 2
  • Shadi Dalili
    • 1
    • 3
  • Tabitha Wood
    • 1
    • 3
  • David Rose
    • 1
    • 2
  • Hong Chang
    • 1
  • Nazir Jamal
    • 1
  • Hans Messner
    • 1
    • 2
    • 4
  • Robert A. Batey
    • 3
  • Aaron D. Schimmer
    • 1
    • 2
    • 4
    Email author
  1. 1.Ontario Cancer InstitutePrincess Margaret HospitalTorontoCanada
  2. 2.The Department of Medical Biophysics, Faculty of MedicineUniversity of TorontoTorontoCanada
  3. 3.The Department of ChemistryUniversity of TorontoTorontoCanada
  4. 4.The Department of Medicine, Faculty of MedicineUniversity of TorontoTorontoCanada

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