Effects of the antitumoural dequalinium on NB4 and K562 human leukemia cell lines

Galeano, Eva; Nieto, Elena; García-Pérez, Ana Isabel; Delgado, M. Dolores; Pinilla, Montserrat; Sancho, Pilar

doi:10.1016/j.leukres.2005.03.014

Cited by 48 publications

(51 citation statements)

References 42 publications

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“…After incubation, cells were washed, lysed, and intracellular MDC fluorescence was measured. Data represent the mean ± SD fluorescence normalized for protein concentration in the lysate of oxidative stress [1][2][3] and activation of the mitochondrial pathway of caspase activation [4][5][6] and inhibition of the topoisomerase I and II enzymes [21,22]. Potentially, some of these effects could lead to the induction of caspase-independent cell death and autophagy.…”

Section: Discussionmentioning

confidence: 99%

“…This pharmacophore is found in a variety of antimicrobial drugs including anti-bacterials, anti-fungals, and antiparasitics. These compounds have multiple mechanisms of action including increasing reactive oxygen species [1][2][3] and disrupting mitochondrial function [4][5][6]. Quinolines also intercalate with DNA and thereby induce DNA damage [7,8].…”

Section: Introductionmentioning

confidence: 99%

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

et al. 2008

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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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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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

et al. 2008

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“…Dequalinium (DQA), a delocalized lipophylic cation, has been proposed as a selective antitumoral agent due to its preferential accumulation in the mitochondria of cancer cells driven by the higher negative electric potential across the mitochondrial membrane in tumor cells as compared with healthy cells [8]. We have shown that DQA induces cytotoxicity in human myeloid leukemia cell lines, with a higher effect in NB4 cells derived from acute promyelocytic leukemia than in K562 cells derived from chronic myeloid leukemia in blastic crisis [9,10]. In the present study, the DQA-induced cytotoxicity in B-cell chronic lymphocytic leukemia (B-CLL) is analyzed by measuring the viability and cell death either by necrosis or apoptosis.…”

Section: Introductionmentioning

confidence: 94%

Dequalinium induces apoptosis in peripheral blood mononuclear cells isolated from human chronic lymphocytic leukemia

et al. 2010

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B-cell chronic lymphocytic leukemia (B-CLL) is an abnormal neoplasic proliferation of B cells, which accumulate mainly in the bone marrow and blood preventing both B cells development in the lymph nodes and the ability to fight against infection. The antitumor agents used in chemotherapy are aimed at inducing malignant cell death, thus limiting the growth and spreading of these cells. However, the lack of specificity for tumor cells exhibited by these agents causes undesirable side effects that have led to the investigation of new therapeutic strategies designed to specifically target malignant cells and thus trigger selective cell destruction. Dequalinium (DQA) is an antitumoral agent that selectively accumulates in the mitochondria and has been shown to display anticancer activity in cells from different malignancies. In the present study, the DQA-induced cytotoxicity in B-CLL cells was analyzed by measuring cell viability and cell death, either by necrosis or apoptosis. Our results support the importance of DQA as a selective and potential antileukemic drug with a higher cytotoxic effect on peripheral blood mononuclear cells from B-CLL patients than in those from healthy donors and encourage the performance of further studies in combination with other agents.

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“…This includes pharyngeal sprays, throat lozenges, mouth washes and decongestant sprays, topical creams, gels, and ointments, as well as tablets or suppositories for vaginal application. Beside its antibacterial activity, dequalinium has been reported to exhibit an array of other biological effects such as potent antitumor activity through toxicity against mitochondria, [8][9][10][11][12] inhibition of protein kinase C, [13,14] antimalarial, [15][16][17] antitrypanosomal, [3,6] and antifungal [7] activities, inhibition of mycothiol ligase in Mycobacterium tuberculosis, [5] selective blockade of small-conductance Ca 2 + -activated K + channels, [18][19][20][21][22][23][24] and disintegration of amyloid fibrils. [25] In addition to these effects, dequalinium's toxicity has also been reported; it may cause skin necrosis if administered on intertriginous skin areas under occlusive conditions.…”

Section: Dequaliniummentioning

confidence: 99%

Quaternary Ammonium Salts and Their Antimicrobial Potential: Targets or Nonspecific Interactions?

et al. 2011

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For more than 50 years dequalinium chloride has been used successfully as an antiseptic drug and disinfectant, particularly for clinical purposes. Given the success of dequalinium chloride, several series of mono- and bisquaternary ammonium compounds have been designed and reported to have improved antimicrobial activity. Furthermore, many of them exhibit high activity against mycobacteria and protozoa, especially against plasmodia. This review discusses the structure-activity relationships and the modes of action of the various series of (bis)quaternary ammonium compounds.

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Effects of the antitumoural dequalinium on NB4 and K562 human leukemia cell lines

Cited by 48 publications

References 42 publications

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

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

Dequalinium induces apoptosis in peripheral blood mononuclear cells isolated from human chronic lymphocytic leukemia

Quaternary Ammonium Salts and Their Antimicrobial Potential: Targets or Nonspecific Interactions?

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