Depletion of drug-surviving glioma cells by a second phase treatment with low concentration of salinomycin

Delwar, Zahid M.; Avramidis, Dimitrios; Sidén, Å; Mabel, Cruz; Yakisich, Juan Sebastián

doi:10.4081/dts.2011.e7

Cited by 7 publications

(9 citation statements)

References 25 publications

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“…However, toxicity may be the main concern. For instance, SAL is very toxic to other normal cells at concentrations effective against cancer stem-like cells [ 166 ] and therefore it is unlikely that this drug will be useful as single agent [ 167 ]. The ability of NIG to induce apoptosis or necrosis by increase K + efflux occurs only at relatively high concentration (2.5–7.5 µM) [ 6 ] that may be not tolerated in vivo.…”

Section: Ionophores In Ongoing Clinical Trials For Cancer Treatmenmentioning

confidence: 99%

Ionophores: Potential Use as Anticancer Drugs and Chemosensitizers

Kaushik

Yakisich

Kumar³

et al. 2018

Cancers

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Ion homeostasis is extremely important for the survival of both normal as well as neoplastic cells. The altered ion homeostasis found in cancer cells prompted the investigation of several ionophores as potential anticancer agents. Few ionophores, such as Salinomycin, Nigericin and Obatoclax, have demonstrated potent anticancer activities against cancer stem-like cells that are considered highly resistant to chemotherapy and responsible for tumor relapse. The preclinical success of these compounds in in vitro and in vivo models have not been translated into clinical trials. At present, phase I/II clinical trials demonstrated limited benefit of Obatoclax alone or in combination with other anticancer drugs. However, future development in targeted drug delivery may be useful to improve the efficacy of these compounds. Alternatively, these compounds may be used as leading molecules for the development of less toxic derivatives.

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Section: Ionophores In Ongoing Clinical Trials For Cancer Treatmenmentioning

confidence: 99%

Ionophores: Potential Use as Anticancer Drugs and Chemosensitizers

Kaushik

Yakisich

Kumar³

et al. 2018

Cancers

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“…After the discovery of salinomycin as an anti‐cancer agent and the suggestion that it has a 100‐fold greater pharmacological effect on cancer stem cells than paclitaxel, several in vitro and in vivo studies have been carried out to evaluate the effects of salinomycin on various cell lines, including cancer and cancer stem cells . In terms of brain tumor therapy, only few studies have shown the effects of salinomycin on glioblastoma cells . Delwar et al reported that tumor cells (glioma DBTRG‐05MG cell line) surviving to hydroxyurea or aphidicolin are slowly depleted by treatment with salinomycin .…”

Section: Introductionmentioning

confidence: 99%

“…In terms of brain tumor therapy, only few studies have shown the effects of salinomycin on glioblastoma cells . Delwar et al reported that tumor cells (glioma DBTRG‐05MG cell line) surviving to hydroxyurea or aphidicolin are slowly depleted by treatment with salinomycin . Calzolari et al investigated the effects of tumor necrosis factor‐related apoptosis‐inducing ligand (TRAIL), salinomycin and the combination of both agents in glioblastoma cell lines and demonstrated that salinomycin enhanced TRAIL‐induced apoptosis, mainly by upregulating the expression of TRAIL‐R2 .…”

Section: Introductionmentioning

confidence: 99%

Salinomycin encapsulated nanoparticles as a targeting vehicle for glioblastoma cells

Aydın

Kaynak

Gümüşderelı́oğlu

2015

J Biomedical Materials Res

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Salinomycin has been introduced as a novel alternative to traditional anti-cancer drugs. The aim of this study was to test a strategy designed to deliver salinomycin to glioblastoma cells in vitro. Salinomycin-encapsulated polysorbate 80-coated poly(lactic-co-glycolic acid) nanoparticles (P80-SAL-PLGA) were prepared and characterized with respect to particle size, morphology, thermal properties, drug encapsulation efficiency and controlled salinomycin-release behaviour. The in vitro cellular uptake of P80-SAL-PLGA (5 and 10 µM) or uncoated nanoparticles was assessed in T98G human glioblastoma cells, and the cell viability was investigated with respect to anti-growth activities. SAL, which was successfully transported to T98G glioblastoma cells via P80 coated nanoparticles (∼14% within 60 min), greatly decreased (p < 0.01) the cellular viability of T98G cells. Substantial morphological changes were observed in the T98G cells with damaged actin cytoskeleton. Thus, P80-SAL-PLGA nanoparticles induced cell death, suggesting a potential therapeutic role for this salinomycin delivery system in the treatment of human glioblastoma.

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“…The effects of salinomycin on brain tumor cells do not have been explored. In this context, a recent study, using the glioma DBTRG-05MG cell line, showed that tumor cells surviving to hydroxyurea or aphidicolin are slowly depleted by treatment with salinomycin [18] .…”

Section: Introductionmentioning

confidence: 99%

Salinomycin Potentiates the Cytotoxic Effects of TRAIL on Glioblastoma Cell Lines

et al. 2014

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Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) has been reported to exhibit therapeutic activity in cancer. However, many tumors remain resistant to treatment with TRAIL. Therefore, small molecules that potentiate the cytotoxic effects of TRAIL could be used for combinatorial therapy. Here we found that the ionophore antibiotic salinomycin acts in synergism with TRAIL, enhancing TRAIL-induced apoptosis in glioma cells. Treatment with low doses of salinomycin in combination with TRAIL augmented the activation of caspase-3 and increased TRAIL-R2 cell surface expression. TRAIL-R2 upmodulation was required for mediating the stimulatory effect of salinomycin on TRAIL-mediated apoptosis, since it was abrogated by siRNA-mediated TRAIL-R2 knockdown. Salinomycin in synergism with TRAIL exerts a marked anti-tumor effect in nude mice xenografted with human glioblastoma cells. Our results suggest that the combination of TRAIL and salinomycin may be a useful tool to overcome TRAIL resistance in glioma cells and may represent a potential drug for treatment of these tumors. Importantly, salinomycin+TRAIL were able to induce cell death of well-defined glioblastoma stem-like lines.

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Depletion of drug-surviving glioma cells by a second phase treatment with low concentration of salinomycin

Cited by 7 publications

References 25 publications

Ionophores: Potential Use as Anticancer Drugs and Chemosensitizers

Ionophores: Potential Use as Anticancer Drugs and Chemosensitizers

Salinomycin encapsulated nanoparticles as a targeting vehicle for glioblastoma cells

Salinomycin Potentiates the Cytotoxic Effects of TRAIL on Glioblastoma Cell Lines

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