Combination effects of alkylphosphocholines and gemcitabine in malignant and normal hematopoietic cells

Georgieva, Milena; Konstantinov, Spiro; Topashka-Ancheva, Margarita; Berger, Martin R.

doi:10.1016/s0304-3835(02)00088-5

Cited by 38 publications

(31 citation statements)

References 24 publications

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“…ErPC is the first APC derivative which can be given intravenously [14]. ErPC has been demonstrated to inhibit proliferation and induce apoptosis of tumor cells, such as brain tumor [14,[18][19][20], lymphoma [6,21,22], leukemia [23], endometrial cancer, and ovarian cancer [24]. However, the effect of ErPC on choriocarcinoma cells has not yet been described.…”

Section: Discussionmentioning

confidence: 99%

RETRACTED ARTICLE: Erucylphosphocholine induces growth inhibition, cell cycle arrest, and apoptosis in human choriocarcinoma cells

et al. 2011

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A membrane-targeted, lipophilic ether lipid of synthetic phospholipid analog, erucylphosphocholine (ErPC), induces apoptosis in some lines of human tumor cells. We investigated the effect of ErPC in the choriocarcinoma cell line, BeWo. BeWo cells were treated with various concentrations of ErPC, and changes in cell growth, the cell cycle, apoptosis, and related parameters were examined. A 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay showed that BeWo cells were sensitive to the growth inhibitory effect of ErPC. Cell cycle analysis indicated that exposure to ErPC decreased the proportion of cells in the S phase and increased the proportion in the G0/G1 phases of the cell cycle. Induction of apoptosis was confirmed by Annexin V staining of externalized phosphatidylserine and by the loss of mitochondrial transmembrane potential. This induction occurred in conjunction with the altered expression of genes related to cell growth, malignant phenotype, and apoptosis. These results suggest that ErPC may serve as a therapeutic agent for the treatment of choriocarcinoma.

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Section: Discussionmentioning

confidence: 99%

RETRACTED ARTICLE: Erucylphosphocholine induces growth inhibition, cell cycle arrest, and apoptosis in human choriocarcinoma cells

et al. 2011

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“…Despite the similarities in the signaling pathways downstream of the mitochondria, ErPC and other synthetic phospholipid analogues displayed no crossresistance towards DNA-damaging drugs or irradiation and even showed additive or synergistic effects in combination experiments in vitro (Noseda et al, 1988;Stekar et al, 1995;Berkovic et al, 1997;Jendrossek et al, 2001;Ruiter et al, 2001;Georgieva et al, 2002). Therefore, these drugs may be particularly useful for the treatment of tumor cells resistant to DNA-damaging drugs or irradiation, as well as for combined treatment protocols.…”

Section: Data Show One Representative Of Three Independent Experimentsmentioning

confidence: 99%

Intracellular mediators of erucylphosphocholine-induced apoptosis

et al. 2003

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Induction of apoptosis contributes to the cytotoxic action of the intravenously applicable alkylphosphocholine erucylphosphocholine (ErPC). To define molecular requirements for ErPC-induced apoptosis, activation of caspases-8, -9 and -3 and cleavage of the caspase-3 substrates PARP and ICAD were tested in normal Jurkat T cells, Jurkat cells resistant to death receptor (CD95 or TNFarelated apoptosis inducing ligand (TRAIL)-induced apoptosis, Jurkat cells lacking caspase-8 or Fas-associated death domain (FADD) Jurkat cells expressing a dominant-negative caspase-9 or overexpressing Bcl-2 as well as BJAB B-lymphoma cells expressing a dominantnegative FADD (FADD-DN). ErPC induced a time-and dose-dependent apoptotic cell death in Jurkat and BJAB cells, which was characterized by breakdown of the phosphatidylserine asymmetry, depolarization of the mitochondrial membrane potential, release of cytochrome c, activation of caspases-9, -8 and -3, cleavage of PARP and ICAD, as well as chromatin condensation. ErPCinduced apoptosis was independent from CD95-receptor signaling and FADD since CD95-and TRAIL-resistant, caspase-8-and FADD-negative Jurkat cells, as well as BJAB cells expressing FADD-DN were sensitive to ErPC-induced apoptosis. In contrast, inhibition of caspase-9 and overexpression of Bcl-2 significantly reduced ErPC-induced caspase activation and apoptosis. Thus, ErPC triggers apoptosis via a Bcl-2-dependent mitochondrial but death receptor-independent pathway.

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“…1,[4][5][6][7] The single drug regimen, such as liposomal DOX, 1,8 gemcitabine (GEM), [9][10][11][12][13][14] and liposomal VCR, 1,15 has been proven to treat B-cell lymphoma in clinical trials. Based on their (DOX, GEM and VCR [DGV]) different mechanisms of action, the combination chemotherapies of DGV are effective and well tolerated in relapse and refractory NHL.…”

Section: Introductionmentioning

confidence: 99%

Lymph cancer chemotherapy: delivery of doxorubicin-gemcitabine prodrug and vincristine by nanostructured lipid carriers

Ni¹,

Qiu²,

Zhang³

et al. 2017

IJN

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Purpose Radiation and chemotherapy are the most common course of treatment for B-cell lymphoma. Doxorubicin (DOX), gemcitabine (GEM), and vincristine (VCR) are the commonly used antilymphoma chemotherapeutic drugs. The aim of this study is to construct a novel drug delivery system for the combination delivery of the three drugs on lymphoma. Materials and methods DOX–GEM prodrug was synthesized. Novel nanostructured lipid carriers (NLCs) containing DOX–GEM prodrug and VCR were prepared and used to treat B-cell lymphoma through in vivo treatment to a lymph cancer animal model. The systemic toxicity of the nanomedicine was also evaluated during the treatment. Results DOX–GEM prodrug and VCR-loaded NLCs (DOX–GEM VCR NLCs) exhibited the highest antitumor effect in B-cell lymphoma cells and lymphoma animal xenografts when compared with the single drug-loaded NLCs and the drug solutions. Conclusion It could be concluded that the highest antitumor effect can be achieved by the system due to the stable drug-loading capacity, attractive anticancer therapeutic effects, and reduced toxicities in human Burkitt’s lymphoma cell line and mice-bearing cancer model. The resulting DOX–GEM VCR NLCs could be an efficient antilymph cancer agent and could be developed further for the treatment of other tumors.

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Combination effects of alkylphosphocholines and gemcitabine in malignant and normal hematopoietic cells

Cited by 38 publications

References 24 publications

RETRACTED ARTICLE: Erucylphosphocholine induces growth inhibition, cell cycle arrest, and apoptosis in human choriocarcinoma cells

RETRACTED ARTICLE: Erucylphosphocholine induces growth inhibition, cell cycle arrest, and apoptosis in human choriocarcinoma cells

Intracellular mediators of erucylphosphocholine-induced apoptosis

Lymph cancer chemotherapy: delivery of doxorubicin-gemcitabine prodrug and vincristine by nanostructured lipid carriers

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