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

Apoptosis : an International Journal on Programmed Cell Death
Rose HurrenAaron D Schimmer

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 (Q(2)). Q(2 )induced cell death in leukemia, myeloma, and solid tumor cell lines with LD50s in the low to submicromolar range. Moreover, Q(2) induced cell death in primary acute myeloid leukemia (AML) cells preferentially over normal hematopoietic cells. In a mouse model of leukemia, Q(2) delayed tumor growth. Mechanistically, Q(2) induced cell death through caspase independent mechanisms. By electron microscopy, Q(2) increased cytoplasmic vacuolization and mitochondrial swelling. Potentially consistent with the induction of autophagic cell death, Q(2) treatment led to a punctate distribution of LC3 and increased MDC staining. Thus, Q(2) is a novel quinolinium with preclinical activity in malignancies such as leukemia and myeloma and warrants further investigation.

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Citations

Jun 26, 2012·Chemical Research in Toxicology·Michael J TwinerGregory J Doucette
May 15, 2012·Haematologica·Lauren I Aronson, Faith E Davies
May 27, 2011·Critical Reviews in Oncology/hematology·Huseyin Atakan EkizYusuf Baran
Aug 2, 2017·The Open Medicinal Chemistry Journal·Christian VélezBeatriz Zayas
Feb 13, 2014·PloS One·Ingeborg Y BartEsther de Vries
Sep 19, 2020·Current Topics in Medicinal Chemistry·Yanna MaoYongfang Yao

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