Carboxymethyl benzylamide dextrans inhibit breast cell growth

Bagheri‐Yarmand, Rozita; Bittoun, Patrick; Champion, J.; Letourneur, Didier; Jozefonvicz, J.; Fermandjian, Serge; Crépin, Michel

doi:10.1007/bf02639391

Cited by 10 publications

(5 citation statements)

References 14 publications

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“…w e hax-e show-n that some dextran derivatix es display ed an in -itro growth inhibitorx activitv on breast pretumour and tumour cells dependinc on their composition ()Mor&re et al 1992: Bagheri-Yarmand et al 1994). For some of them.…”

mentioning

confidence: 99%

The suppression of fibroblast growth factor 2/fibroblast growth factor 4-dependent tumour angiogenesis and growth by the anti-growth factor activity of dextran derivative (CMDB7)

Bagheri‐Yarmand

Kourbali²,

Mabilat³

et al. 1998

Br J Cancer

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Summary Our previous studies showed that carboxymethyl benzylamide dextran (CMDB7) blocks basic fibroblast growth factor (FGF-2)-dependent cell proliferation of a human breast epithelial line (HBL1 00), suggesting its potential role as a potent antiangiogenic substance. The derived cell line (HH9), which was transformed with the hst/FGF4 gene, has been shown to be highly proliferative in vitro and to induce angiogenic tumours in nude mice. We show here that CMDB7 inhibits the mitogenic activities of the conditioned media from HBL 100 and HH9 cells in a dose-dependent manner. When HH9 cells were injected s.c. into nude mice, CMDB7 treatment (300 mg kg-' week-') suppressed the tumour take and the tumour growth by about 5Oi/o and 80% respectivety. Immunohistochemical analysis showed a highly significant decrease, by more than threefold, in the endothelial density of viable tumour regions, together with a significant increase in the necrosis area. This antiangiogenic activity of CMDB7 was further demonstrated by direct inhibition of calf pulmonary artery (CPAE) and human umbilical vein (HUVEC) endothelial cell proliferation and migration in vitro. In addition, we showed that CMDB7 inhibits specifically the mitogenic effects of the growth factors that bind to hepann such as FGF-2, FGF-4, platelet-derived growth factor (PDGF-BB) and transforming growth factor (TGF-p1), but not those of epidermal growth factor (EGF) and insulin-like growth factor (IGF-1). These results demonstrate that CMDB7 inhibits FGF-2/FGF-4-dependent tumour growth and angiogenesis, most likety by disrupting the autocrine and paracrine effects of growth factors released from the tumour cells.

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mentioning

confidence: 99%

The suppression of fibroblast growth factor 2/fibroblast growth factor 4-dependent tumour angiogenesis and growth by the anti-growth factor activity of dextran derivative (CMDB7)

Bagheri‐Yarmand

Kourbali²,

Mabilat³

et al. 1998

Br J Cancer

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“…Previous work has shown that such dextran derivatives displayed an in vitro growthinhibitory activity on breast pretumoral and tumoral cells, depending on their composition. 16,18 NaPA was found to potentiate the antitumor activity of suramin, a drug acting through different mechanisms. 6 Our study shown that the human melanoma cell phenotype was sensitive to NaPA.…”

Section: Discussionmentioning

confidence: 98%

“…This effect confirms the results obtained with other tumoral cells. 15,18 A low but detectable inhibitory effect appears at a concentration of 37 mM (10 mg/ml) of LS17-DMCB. The absence of effect with the precursors, T40 Dextran and LS17-DMC, indicates that benzylamide groups linked to glucosyl units of dextran are required to promote cell growth inhibition.…”

Section: Discussionmentioning

confidence: 98%

“…The results indicated that the chemical nature and the proportion of groups linked to glucosyl units of the dextran chains are required to promote cell growth inhibition. 18 In addition, we showed that CMDB7 prevents tumor angiogenesis by binding to angiogenic growth factors and leading to non-activation of their receptors. 17,19 In addition, previous works show that the mechanism of CMDB7 activity involves cytokines sequestering.…”

Section: Introductionmentioning

confidence: 97%

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Growth inhibition of human melanoma tumor cells by the combination of sodium phenylacetate (NaPA) and substituted dextrans and one NaPA–dextran conjugate

Gervelas

Avramoglou²,

Crépin³

et al. 2002

Anti-Cancer Drugs

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We have studied the cytostatic effects of sodium phenylacetate (NaPA) in association with several substituted dextrans on human tumor melanoma 1205LU cells. We show that NaPA alone inhibits the growth of these cells (IC50 = 3.9 mM) while a weak inhibitory effect appears at a concentration of 37 microM (10 microg/ml) for a dextran methyl carboxylate benzylamide (LS17-DMCB). The precursors of LS17-DMCB [T40 Dextran and carboxymethyl dextran (LS17-DMC)] did not affect the growth of 1205LU cells. To potentiate the inhibitory activity of NaPA at low concentrations (below 5.6 mM), we have tested NaPA and LS17-DMCB in physical mixture (association) or linked together covalently (this conjugate is termed 'LS17-NaPaC'). We have observed an increase of the 1205LU cell growth inhibition effect with NaPA in association (IC50 1.8 mM). For a concentration of 5 mM of NaPA (free in the case of association or linked in the case of conjugate), the association with dextran derivative exhibits a 4.6-fold higher efficacy than with NaPA alone (9 versus 41% surviving fraction), while the conjugate is 1.3-fold smaller (52% growth inhibition). By performing isobologram analysis of the IC50 data, we have shown a synergistic effect for a particular molar ratio of NaPA and LS17-DMCB (NaPA:LS17-DMCB = 0.35).

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“…The proliferative nature is not related to the anticoagulant properties [109,288]. Some CMDB derivates exhibit an inhibitory effect on human breast cancer lines [296][297][298]. The inhibitory effect on cell growth appears to be independent of the sulfate and sulfonate groups but depends rather on the benzylamide content.…”

Section: Bioactivity Of Cmd-based Derivatives (Heparan Sulfate Mimetics)mentioning

confidence: 99%

Functional Polymers Based on Dextran

Heinze

Liebert

Heublein

et al.

Advances in Polymer Science

248

198

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Dextran, comprising a family of neutral polysaccharides consisting of an α-(1→6) linked d-glucose main chain with varying proportions of linkages and branches, depending on the bacteria used, is an interesting starting material for chemical modification reactions for the design of new functional polymers with promising properties. The review summarises recent results on structure characterisation of dextran including some comments on biosynthesis of this important class of biopolymers. Applications of dextran are discussed as well. Chemical modification reactions of dextran are increasingly studied for the structure and hence property design. The review highlights recent progress in esterification of dextran, both inorganic and organic polysaccharide esters, etherification reactions towards ionic and non-ionic ethers, and the huge variety of different conversions mainly developed for the binding of drugs. It summarises recent developments in the application of dextran derivatives with a focus on the chemical structures behind these materials such as prodrugs, bioactivity of inorganic dextran esters, heparin sulfate mimics, hydrogels, nanoparticles and self assembly structures for surface modification. Keywords Functionalised dextran • Structural analysis • Prodrugs • Nanostructures • Bioactivity Abbreviations AFM Atomic force microscopy AGU Anhydroglucose units AT Antithrombin AZT Azidothymidine BSH Na 2 B 12 H 11 SH BSA Bovine serum albumin CAC Critical association concentration CDI N,N -Carbonyldiimidazole CMC Critical micelle concentration CMD Carboxymethyl dextran CMDB Carboxymethyl dextran benzylamide CMDBSSu Carboxymethyl dextran benzylamidesulfonate sulfate CMDBSu Carboxymethyl dextran benzylamide sulfate CMDEE Carboxymethyl dextran ethyl ester CMDSu Carboxymethyl dextran sulfate COSY Two-dimensional correlated spectroscopy CsA Cyclosporin A 2D Two-dimensional Dach-Pt cis-Dihydroxo(cyclohexane-trans-l-1,2-diamine)platinum II DCC N,N -Dicyclohexylcarbodiimide T. Heinze et al.

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Carboxymethyl benzylamide dextrans inhibit breast cell growth

Cited by 10 publications

References 14 publications

The suppression of fibroblast growth factor 2/fibroblast growth factor 4-dependent tumour angiogenesis and growth by the anti-growth factor activity of dextran derivative (CMDB7)

The suppression of fibroblast growth factor 2/fibroblast growth factor 4-dependent tumour angiogenesis and growth by the anti-growth factor activity of dextran derivative (CMDB7)

Growth inhibition of human melanoma tumor cells by the combination of sodium phenylacetate (NaPA) and substituted dextrans and one NaPA–dextran conjugate

Functional Polymers Based on Dextran

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