Monoglycerides induce apoptosis in human leukemic cells while sparing normal peripheral blood mononuclear cells

Philippoussis, Fabianne; Arguin, Chantal; Mateo, Véronique; Steff, Ann‐Muriel; Hugo, Patrice

doi:10.1182/blood-2002-03-0894

Cited by 7 publications

(4 citation statements)

References 15 publications

(17 reference statements)

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“…Several recent studies have identified drugs that show selectivity toward CLL cells compared to normal T cells. [13][14][15][16][17][18][19][20][21][22][23] However, the actions of these agents on bone marrow progenitor cells was not investigated. Importantly, we have shown here that GA did not induce apoptosis of CD34 ϩ progenitor cells from normal bone marrow and may even confer a modest cytoprotective effect.…”

Section: Discussionmentioning

confidence: 99%

“…11,12 Therefore, there has been considerable interest in identifying novel drugs that induce CLL apoptosis with greater selectivity. [13][14][15][16][17][18][19][20][21][22][23][24] Deletion of the p53 tumor suppressor gene, whose protein product is a key mediator of drug-induced apoptosis, predicts a poor response to cytotoxic drugs. 25,26 However, even CLL cells harboring intact p53 genes may be defective in p53-mediated apoptosis, resulting from the inactivation of the ATM protein kinase pathway, [27][28][29][30] which links DNA damage induction to p53 up-regulation.…”

Section: Introductionmentioning

confidence: 99%

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Geldanamycin and herbimycin A induce apoptotic killing of B chronic lymphocytic leukemia cells and augment the cells' sensitivity to cytotoxic drugs

Jones

Addison

North

et al. 2004

Blood

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IntroductionB chronic lymphocytic leukemia (CLL) is characterized by the clonal expansion of CD5 ϩ CD19 ϩ B-lymphoid cells. Although CLL cells proliferate slowly, defective apoptosis results in progressive accumulation of the malignant clone. [1][2][3] The clinical course of CLL is highly variable. Although a proportion of patients survive for extended periods without the need for clinical intervention, others undergo rapid disease progression and require aggressive treatment. Recent studies have established that a subset of patients with CLL with unmutated immunoglobulin heavy chain variable (IgV H ) genes have an inferior clinical outcome compared to the subset with mutated IgV H genes. 4,5 Furthermore, expression of the protein tyrosine kinase ZAP-70 correlates well with an unmutated IgV H status, providing an accessible alternative criterion for the management of patients with CLL. [6][7][8] There is an urgent need to develop novel protocols for the treatment patients with a poor prognosis identified by IgV H mutation analysis or ZAP-70 expression.For many years, the nitrogen mustard chlorambucil has been the drug of choice in CLL. More recently, the nucleoside analog fludarabine has proved useful, especially for the treatment of patients who fail to respond to chlorambucil. 9 Although high remission rates have been achieved using this drug, 10 myelosuppression has proved to be a critical dose-limiting factor. 11 Fludarabine is also highly toxic to T lymphocytes and results in prolonged depression of CD4 ϩ T cells, increasing the risk of opportunistic infections. 11,12 Therefore, there has been considerable interest in identifying novel drugs that induce CLL apoptosis with greater selectivity. [13][14][15][16][17][18][19][20][21][22][23][24] Deletion of the p53 tumor suppressor gene, whose protein product is a key mediator of drug-induced apoptosis, predicts a poor response to cytotoxic drugs. 25,26 However, even CLL cells harboring intact p53 genes may be defective in p53-mediated apoptosis, resulting from the inactivation of the ATM protein kinase pathway, 27-30 which links DNA damage induction to p53 up-regulation. Because of the limitations of existing therapeutic options, [9][10][11][12][25][26][27][28][29][30] it is important to evaluate drugs that induce apoptosis of CLL cells via actions on novel cellular targets. 24 Optimal new drugs would display a high degree of selectivity for the malignant cells while sparing hematopoietic progenitors and T lymphocytes. Further advantageous characteristics include a p53-independent mode of action and synergistic actions with conventional cytotoxic drugs.The ansamycin antibiotics geldanamycin (GA) and herbimycin A (HMA) have attracted interest as potential anticancer agents. 31,32 These drugs target the adenosine triphosphate (ATP)-binding pocket of the cytosolic chaperone heat shock protein 90 (Hsp90). 33 Hsp90 ensures maintenance of the correctly folded conformation of a range of client proteins involved in signal transduction, including Akt, Raf-1, Erb B2, and...

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Geldanamycin and herbimycin A induce apoptotic killing of B chronic lymphocytic leukemia cells and augment the cells' sensitivity to cytotoxic drugs

Jones

Addison

North

et al. 2004

Blood

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“…The initial bioassay-guided fractionation work was performed using DLD-1 colon adenocarcinoma cells. These compounds were also tested for activity versus two other cell lines, KYSE-30 (esophageal squamous cancer) and NCI-N87 (gastric carcinoma), and compared with the positive controls glycerol monopalmitate 15,16 and the anticancer drug 5-fluorouracil. The results are shown in Table 5 and confirm the high level of activity in these assays for the acylglycerols.…”

Section: Journal Of Natural Productsmentioning

confidence: 99%

Antiproliferative Acylated Glycerols from New Zealand Propolis

et al. 2019

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Previous work has shown that a number of phenolic components of NZ propolis possess antiproliferative activity against certain human gastrointestinal cancer cell lines.Here we report on a series of acylglycerols isolated from the nonpolar fraction of propolis resin, which represent further bioactive constituents unrelated to the more usual phenolic compounds generally found in propolis. NZ propolis is sourced from poplar trees, and the acylglycerols have been shown to be present in the leaves and buds of some common poplars. The compounds are a series of monoglycerides containing 3,8-dihydroxy fatty acids, many of which are further acylated with acetic acid residues. The dihydroxy fatty acids are C 18 to C 24 , with the most abundant being C 20 and C 22 . These acylglycerols were found to have strong antiproliferative activity against three human gastrointestinal cell lines, particularly gastric cancer cell line NCI-N87, where one example shows an IC 50 of less than 50 μM.

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“…This property allows them to be used in various fields of the food industry [1]. In addition to showing emulsifying properties, MAGʼs have also been reported to show anticancer properties by their ability to induce apoptosis of human leukemic cells [2] and cervical cancer cells [3], with no cytotoxicity effect to normal human cells [2]. Moreover, MAGs also exhibit inhibitory effects against some types of microorganisms.…”

Section: Introductionmentioning

confidence: 99%

Encapsulation of Bioactive Compounds (Monocaprin and Monolaurin) into Polymeric Nanoparticles

Kaewmanee

Wongsatayanon

Durand

2018

MSF

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The dextran-covered poly (lactic acid) (PLA) polymeric nanoparticles were prepared by a nanoprecipitation process for the encapsulation of monocaprin (MC) or monolaurin (ML). The concentration of PLA/MC or ML was varied to evaluate the best condition for preparation. The miscibility of various PLA/MC or ML blends was studied using differential scanning calorimetry. The result showed that at concentrations of 50/50 wt/wt, the PLA/ML blend was partly miscible and the nanoparticle suspension produced large amounts of macroscopic aggregates after nanoprecipitation. Conversely, the miscibility of PLA/MC blends progressively increased with increasing amounts of PLA. Therefore, the best concentration to encapsulate the MC was the PLA/MC 90/10 (wt/wt), according to the miscibility results.

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Monoglycerides induce apoptosis in human leukemic cells while sparing normal peripheral blood mononuclear cells

Cited by 7 publications

References 15 publications

Geldanamycin and herbimycin A induce apoptotic killing of B chronic lymphocytic leukemia cells and augment the cells' sensitivity to cytotoxic drugs

Geldanamycin and herbimycin A induce apoptotic killing of B chronic lymphocytic leukemia cells and augment the cells' sensitivity to cytotoxic drugs

Antiproliferative Acylated Glycerols from New Zealand Propolis

Encapsulation of Bioactive Compounds (Monocaprin and Monolaurin) into Polymeric Nanoparticles

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