Combining suramin and a chimeric toxin directed to basic fibroblast growth factor receptors increases therapeutic efficacy against human melanoma in an animal model

Davol, Pamela A.; Garza, Scott J.; Frackelton, A. Raymond

doi:10.1002/(sici)1097-0142(19991101)86:9<1733::aid-cncr15>3.0.co;2-h

Cited by 14 publications

(7 citation statements)

References 37 publications

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“…Moreover, recombinant basic FGF-saporin fusion also showed significant anti-proliferation activity when tested in animal models of human ovarian teratocarcinoma or melanomas in a combination therapy [131,132]. Another example of a fully recombinant saporin fusion is represented by an EGF receptor-targeted fusion between a heparin-binding epidermal growth factor (HEGF) and saporin, showing selective cytotoxic activity towards human breast carcinoma cells [133].…”

Section: Immunotoxins and Targeted Chimeric Toxinsmentioning

confidence: 99%

Ribosome-Inactivating Proteins: From Plant Defense to Tumor Attack

Virgilio

Lombardi

Caliandro

et al. 2010

Toxins

145

128

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Ribosome-inactivating proteins (RIPs) are EC3.2.32.22 N-glycosidases that recognize a universally conserved stem-loop structure in 23S/25S/28S rRNA, depurinating a single adenine (A4324 in rat) and irreversibly blocking protein translation, leading finally to cell death of intoxicated mammalian cells. Ricin, the plant RIP prototype that comprises a catalytic A subunit linked to a galactose-binding lectin B subunit to allow cell surface binding and toxin entry in most mammalian cells, shows a potency in the picomolar range. The most promising way to exploit plant RIPs as weapons against cancer cells is either by designing molecules in which the toxic domains are linked to selective tumor targeting domains or directly delivered as suicide genes for cancer gene therapy. Here, we will provide a comprehensive picture of plant RIPs and discuss successful designs and features of chimeric molecules having therapeutic potential.

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Section: Immunotoxins and Targeted Chimeric Toxinsmentioning

confidence: 99%

Ribosome-Inactivating Proteins: From Plant Defense to Tumor Attack

Virgilio

Lombardi

Caliandro

et al. 2010

Toxins

145

128

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“…FGF-protein toxins have demonstrated efficacy against a variety of tumour types and have been shown to inhibit the growth of metastasis as well as established tumours. Combination therapy, where FGF-protein toxins are used in conjunction with compounds such as wortmannin [107] or suramin [167], has demonstrated the benefits of this approach. It may also be advantageous to combine multiple FGF-toxins, each possessing a different FGFR specificity (e.g., FGF-1-toxin plus FGF-2-toxin), to reduce the chances of resistance due to either tumour heterogeneity or receptor downregulation with respect to a specific FGFR [164].…”

Section: Toxin Delivery With Fgfsmentioning

confidence: 99%

Fibroblast growth factors in cancer: therapeutic possibilities

Jeffers¹,

LaRochelle²,

Lichenstein³

2002

Expert Opinion on Therapeutic Targets

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The fibroblast growth factor (FGF) family of signalling molecules and its receptors (FGFRs) contribute to normal developmental and physiological processes. However, the subversion of this powerful growth stimulatory pathway has been implicated in the generation of a variety of pathological conditions. This review focuses on the role of FGF/FGFRs in cancer. The case will be made that this signalling pathway is associated with and functionally important for the growth of some human tumours. As such, FGF/FGFRs can be viewed as rational therapeutic oncology targets and strategies used to inhibit these molecules are discussed. The therapeutic exploitation of tumour-associated FGFR expression to deliver toxins or antiproliferative signals to tumour cells is also reviewed, as is the use of FGFs as protein therapeutics to alleviate the side effects of cancer therapy.

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“…Many of suramin's actions have clinical relevance. For example, suramin inhibits the binding of several growth factors (such as PDGF, TGF-β, fibroblast growth factor, insulin-like growth factor and EGF) to their cell surface receptors and this property of suramin is related to its anti-tumour actions (Sullivan et al, 1997;Davol et al, 1999;Kathir et al, 2006;McGeary et al, 2008). Suramin also has antiviral actions and has been used for human immunodeficiency virus infection (Voogd et al, 1993;Kreimeyer et al, 1998).…”

Section: Introductionmentioning

confidence: 99%

Suppression of cell membrane permeability by suramin: involvement of its inhibitory actions on connexin 43 hemichannels

Chi

Gao

Zhang

et al. 2014

British J Pharmacology

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BACKGROUND AND PURPOSESuramin is a clinically prescribed drug for treatment of human African trypanosomiasis, cancer and infection. It is also a well-known pharmacological antagonist of P2 purinoceptors. Despite its clinical use and use in research, the biological actions of this molecule are still incompletely understood. Here, we investigated the effects of suramin on membrane channels, as exemplified by its actions on non-junctional connexin43 (Cx43) hemichannels, pore-forming α-haemolysin and channels involved in ATP release under hypotonic conditions. EXPERIMENTAL APPROACHHemichannels were activated by removing extracellular Ca 2+. The influences of suramin on hemichannel activities were evaluated by its effects on influx of fluorescent dyes and efflux of ATP. The membrane permeability and integrity were assessed through cellular retention of preloaded calcein and LDH release. KEY RESULTSSuramin blocked Cx43 hemichannel permeability induced by removal of extracellular Ca 2+ without much effect on Cx43 expression and gap junctional intercellular communication. This action of suramin was mimicked by its analogue NF023 and NF449 but not by another P2 purinoceptor antagonist PPADS. Besides hemichannels, suramin also significantly blocked intracellular and extracellular exchanges of small molecules caused by α-haemolysin from Staphylococcus aureus and by exposure of cells to hypotonic solution. Furthermore, it prevented α-haemolysin-and hypotonic stress-elicited cell injury. CONCLUSION AND IMPLICATIONSSuramin blocked membrane channels and protected cells against toxin-and hypotonic stress-elicited injury. Our finding provides novel mechanistic insights into the pharmacological actions of suramin. Suramin might be therapeutically exploited to protect membrane integrity under certain pathological situations. AbbreviationsCx43, connexin 43; EtBr, ethidium bromide; GJIC, gap junctional intercellular communication; LY, Lucifer yellow; NRK, Normal rat kidney; PPADS, pyridoxalphosphate-6-azophenyl-2′,4′-disulfonic acid

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Combining suramin and a chimeric toxin directed to basic fibroblast growth factor receptors increases therapeutic efficacy against human melanoma in an animal model

Cited by 14 publications

References 37 publications

Ribosome-Inactivating Proteins: From Plant Defense to Tumor Attack

Ribosome-Inactivating Proteins: From Plant Defense to Tumor Attack

Fibroblast growth factors in cancer: therapeutic possibilities

Suppression of cell membrane permeability by suramin: involvement of its inhibitory actions on connexin 43 hemichannels

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