A novel diquinolonium displays preclinical anti-cancer activity and induces caspase-independent cell death
| Autor: | Nazir Jamal, Hong Chang, Shadi Dalili, Tabitha E. Wood, Rose Hurren, Reza Beheshti Zavareh, Robert A. Batey, Hans A. Messner, David R. Rose, Aaron D. Schimmer |
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| Rok vydání: | 2008 |
| Předmět: |
Cancer Research
Programmed cell death Cell Survival Clinical Biochemistry Pharmaceutical Science Biology Jurkat cells Amino Acid Chloromethyl Ketones Lethal Dose 50 Jurkat Cells Mice hemic and lymphatic diseases Cell Line Tumor medicine Autophagy Tumor Cells Cultured Animals Humans Pharmacology U937 cell Cell Death Quinolinium Compounds Biochemistry (medical) Myeloid leukemia Cell Biology U937 Cells medicine.disease Leukemia Lymphocytic Chronic B-Cell Cell biology Haematopoiesis Leukemia Leukemia Myeloid Acute Apoptosis Cell culture Mice Inbred DBA Caspases Cancer research HeLa Cells |
| Zdroj: | Apoptosis : an international journal on programmed cell death. 13(6) |
| ISSN: | 1573-675X |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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