Salinomycin Effects on Mitochondrial Ion Translocation and Respiration

Mitani, Mitsuaki; Yamanishi, Tadashi; Miyazaki, Y.; Ōtake, Noboru

doi:10.1128/aac.9.4.655

Cited by 98 publications

(86 citation statements)

References 26 publications

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“…24 SAM stimulates alkali cation transport and thus inhibits oxidative phosphorylation in the rat liver mitochondria. 25 An impairment of mitochondrial electron transport function can be a cause of mitochondrial reactive oxygen species generation, and this intracellular oxidative stress may consequently enhance plasma membrane phospholipid peroxidation, as in the case with allicin-dependent cellular uptake of PMB. 26,27 The effects of SAM and MON on the cellular uptake of PMB were therefore examined by measuring the extracellular concentration of PMB by HPLC analysis.…”

Section: Resultsmentioning

confidence: 99%

Synergistic fungicidal activities of polymyxin B and ionophores, and their dependence on direct disruptive action of polymyxin B on fungal vacuole

et al. 2009

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Polymyxin B (PMB) acts selectively on Gram-negative bacteria by electrostatic and hydrophobic interactions with anionic cell envelope components such as phospholipids and lipopolysaccharides. In this study, PMB was shown to exhibit marked fungicidal activity against yeasts and filamentous fungi in combination with ionophores such as salinomycin (SAM) and monensin (MON), which can selectively interact with monovalent cations. Ca 2+ -selective ionophores, A23187 and ionomycin, were absolutely ineffective in enhancing the fungicidal activity of PMB. SAM and MON increased the rate of cellular uptake of PMB possibly in favor of its intracellular action on the organelle. PMB could indeed directly disrupt the spherical membraneenclosed architecture of the isolated vacuoles equally in the absence and presence of the ionophores. The loss of energy barrier for transmembrane transport of monovalent cations is considered to be a cause of enhanced incorporation of larger cationic compounds such as PMB across fungal plasma membrane.

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Section: Resultsmentioning

confidence: 99%

Synergistic fungicidal activities of polymyxin B and ionophores, and their dependence on direct disruptive action of polymyxin B on fungal vacuole

et al. 2009

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“…Salinomycin is a 751-Da monocarboxylic polyether antibiotic, which was initially used to eliminate bacteria, fungi and parasites and is fed to ruminants to improve nutrient absorption and feeding efficiency (15,16). This compound is now considered an important anticancer drug candidate (17,18).…”

Section: Introductionmentioning

confidence: 99%

“…Most modern treatments are ineffective against solid tumors and this may be the result of the increased resistance of CSCs (13). Therefore, it is vital to find novel therapeutic methods to eradicate CSCs and enable the development of more effective treatment protocols (14).Salinomycin is a 751-Da monocarboxylic polyether antibiotic, which was initially used to eliminate bacteria, fungi and parasites and is fed to ruminants to improve nutrient absorption and feeding efficiency (15,16). This compound is now considered an important anticancer drug candidate (17,18).…”

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confidence: 99%

Salinomycin inhibits the growth of colorectal carcinoma by targeting tumor stem cells

Zhang

Tian

Song³

et al. 2015

Oncology Reports

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Abstract. Salinomycin is a monocarboxylic polyether antibiotic that has been reported to induce apoptosis in various types of cancer cells with specificity for cancer stem cells. However, its anticancer effect in colorectal cancer stem cells has never been reported. In the present study, we examined the ability of salinomycin to induce cell death in the colorectal cancer stem cell line CD44 + EpCAM + HCT-116, and we measured its in vivo tumor inhibition capacity. Salinomycin dose-dependently induced cytotoxicity in the CD44 + EpCAM + HCT-116 cells and inhibited colony formation. Salinomycin treatment was shown to induce apoptosis, as evidenced by nuclear fragmentation, an increase in the proportion of acridine orange/ethidium bromide-positive cells and an increase in the percentage of Annexin V-positive cells. Apoptosis was induced in colorectal cancer stem cells in a caspase-dependent manner, as shown by an increase in the levels of cleaved caspase-3, -8 and -9. JC-1 staining further revealed that salinomycin induced colorectal cancer cell apoptosis via the mitochondrial pathway. In addition, salinomycin treatment of xenograft mice inhibited the growth of tumors derived from the CD44 + EpCAM + HCT-116 cells. The present study demonstrated that the antibiotic salinomycin exerts an anti-colorectal cancer effect in vitro and in vivo, suggesting salinomycin as a potential drug for colorectal cancer therapy. IntroductionColorectal cancer (CRC) is the third most common malignancy worldwide, accounting for ~10% of all cancer cases and CRC is one of the most common causes of death related to gastrointestinal cancers (1-3). Although the incidence rates of colon cancer have declined somewhat, current therapies are associated with serious side-effects, high cost and recurrence rates exceeding 50%, primarily due to the development of acquired chemoresistance to conventional chemotherapeutics (4,5).Emerging data suggest that malignant tumors contain a small distinct population of cancer stem cells (CSCs), which are responsible for tumor initiation and propagation (6). Stem cell research and the cancer stem cell (CSC) hypothesis have shown that colonic stem cells or CSCs are involved in tissue regeneration and colonic carcinogenesis (7-9). Drug-resistant CSCs are thought to be one of the key causes of CRC treatment failure, and it is hypothesized that these cells are ultimately the likely cause of metastasis and tumor recurrence (10-12). Most modern treatments are ineffective against solid tumors and this may be the result of the increased resistance of CSCs (13). Therefore, it is vital to find novel therapeutic methods to eradicate CSCs and enable the development of more effective treatment protocols (14).Salinomycin is a 751-Da monocarboxylic polyether antibiotic, which was initially used to eliminate bacteria, fungi and parasites and is fed to ruminants to improve nutrient absorption and feeding efficiency (15,16). This compound is now considered an important anticancer drug candidate (17,18). It has recently been reporte...

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“…It is a lipophilic, anionic and weakly acidic compound with the molecular formula c 42 H 70 o 11 (1,2). Salinomycin acts in different biological membranes, including cytoplasmic and mitochondrial membranes, as a ionophore with strict selectivity for alkali ions and a strong preference for potassium, thereby promoting mitochondrial and cellular potassium efflux and inhibiting mitochondrial oxidative phosphorylation (3)(4)(5).…”

Section: Introductionmentioning

confidence: 99%

Salinomycin in cancer: A new mission for an old agent

Naujokat

Fuchs²,

Opelz³

2010

Mol Med Rep

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Abstract. Salinomycin is a monocarboxylic polyether ionophore isolated from Streptomyces albus that has been used for more than 30 years as an agricultural antibiotic to prevent coccidiosis in poultry and to improve nutrient absorption and feed efficiency in ruminants and swine. As a inonophore with strict selectivety for alkali ions and a strong preference for potassium, salinomycin interferes with transmembrane potassium potential and promotes the efflux of K

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Salinomycin Effects on Mitochondrial Ion Translocation and Respiration

Cited by 98 publications

References 26 publications

Synergistic fungicidal activities of polymyxin B and ionophores, and their dependence on direct disruptive action of polymyxin B on fungal vacuole

Synergistic fungicidal activities of polymyxin B and ionophores, and their dependence on direct disruptive action of polymyxin B on fungal vacuole

Salinomycin inhibits the growth of colorectal carcinoma by targeting tumor stem cells

Salinomycin in cancer: A new mission for an old agent

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