The inhibitory effect of salinomycin on the proliferation, migration and invasion of human endometrial cancer stem-like cells

Kusunoki, Soshi; Kato, Kanefusa; Tabu, Kouichi; Inagaki, Takeshi; Okabe, Hikaru; Kuroda, Hiroshi; Suga, Shin Ichi; Terao, Yasuhisa; Taga, Tetsuya; Takeda, Satoru

doi:10.1016/j.ygyno.2013.03.005

Cited by 76 publications

(62 citation statements)

References 31 publications

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“…Downregulation of BCL-XL by salinomycin was also observed in colorectal cancer cells (Zhou et al 2013) and in primary culture cells of human uterine leiomyoma (Lee et al 2014). Our results are also consistent with those of other studies reporting the induction of apoptosis and decreased expression of BCL-2 following exposure to salinomycin (Kusunoki et al 2013;Lee et al 2014). Conversely, increased expression of BAK occurred in the non-tumor cell line HB4a, albeit with reduced expression of CASP9, which may have prevented the induction of the apoptotic cascade in those cells.…”

Section: Discussionsupporting

confidence: 92%

Salinomycin efficiency assessment in non-tumor (HB4a) and tumor (MCF-7) human breast cells

Niwa

D’Epiro

Marques

et al. 2016

Naunyn-Schmiedeberg's Arch Pharmacol

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The search for anticancer drugs has led researchers to study salinomycin, an ionophore antibiotic that selectively destroys cancer stem cells. In this study, salinomycin was assessed in two human cell lines, a breast adenocarcinoma (MCF-7) and a non-tumor breast cell line (HB4a), to verify its selective action against tumor cells. Real-time assessment of cell proliferation showed that HB4a cells are more resistant to salinomycin than MCF-7 tumor cell line, and these data were confirmed in a cytotoxicity assay. The half maximal inhibitory concentration (IC50) values show the increased sensitivity of MCF-7 cells to salinomycin. In the comet assay, only MCF-7 cells showed the induction of DNA damage. Flow cytometric analysis showed that cell death by apoptosis/necrosis was only induced in the MCF-7 cells. The increased expression of GADD45A and CDKN1A genes was observed in all cell lines. Decreased expression of CCNA2 and CCNB1 genes occurred only in tumor cells, suggesting G2/M cell cycle arrest. Consequently, cell death was activated in tumor cells through strong inhibition of the antiapoptotic genes BCL-2, BCL-XL, and BIRC5 genes in MCF-7 cells. These data demonstrate the selectivity of salinomycin in killing human mammary tumor cells. The cell death observed only in MCF-7 tumor cells was confirmed by gene expression analysis, where there was downregulation of antiapoptotic genes. These data contribute to clarifying the mechanism of action of salinomycin as a promising antitumor drug and, for the first time, we observed the higher resistance of HB4a non-tumor breast cells to salinomycin.

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Section: Discussionsupporting

confidence: 92%

Salinomycin efficiency assessment in non-tumor (HB4a) and tumor (MCF-7) human breast cells

Niwa

D’Epiro

Marques

et al. 2016

Naunyn-Schmiedeberg's Arch Pharmacol

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“…Eradication of these CSCs, however, has proven difficult, partly because several protection mechanisms are operative in these cells [11,25]. In the face of this challenge, the demonstration that IAs can target various CSC populations (including populations expressing ABCB1 and ABCG2) [3][4][5][6][7][8]12] was particularly remarkable. Despite this, a definite role of drug transporters in the response to IA-based treatment has not been established.…”

Section: Discussionmentioning

confidence: 99%

“…Based on the reported abilities of IAs to bear selectivity against epithelial and nonepithelial CSCs [3][4][5][6][7][8] and to overcome transporter-mediated drug resistance [12], we tested their effects on OvCa SP cells; however, using different cell lines expressing either ABCB1 or ABCG2, we found that-in contrast to non-SP cells-viability of SP cells was only marginally affected by salinomycin and nigericin (Fig. 3A, 3B) (data not shown).…”

Section: Ias Are Ineffective Against Stem-like Sp Cellsmentioning

confidence: 99%

Drug Transporter-Mediated Protection of Cancer Stem Cells From Ionophore Antibiotics

Boesch

Zeimet

Rumpold

et al. 2015

Stem Cells Translational Medicine

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Ionophore antibiotics were reported to selectively kill cancer stem cells and to overcome multidrug resistance, but mechanistic studies of the significance of drug transporters for treatment with these compounds are lacking. We applied chemosensitivity testing of well-characterized human cancer cell lines to elaborate on whether drug transporters are involved in protection from the cytotoxic effects of the ionophore antibiotics salinomycin and nigericin. Our experiments demonstrated that ionophore antibiotics were ineffective against both stem-like ovarian cancer side population cells (expressing either ABCB1 or ABCG2) and K562/Dox-H1 cells, which constitute a genetically defined model system for ABCB1 expression. Considering that cancer stem cells often express high levels of drug transporters, we deduced from our results that ionophore antibiotics are less suited to cancer stem cell-targeted treatment than previously thought. STEM CELLS

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“…BCL2 contributes a crucial role in cell death, apoptosis, migration and invasion (3,9,23,24). Previous studies have reported that BCL2 is involved in the pathogenesis of laryngeal cancer (10)(11)(12).…”

Section: Discussionmentioning

confidence: 99%

MiR-34c induces apoptosis and inhibits the viability of M4e cells by targeting BCL2

Zhang

Zheng

2017

Oncol Lett

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Abstract. The present study aimed to investigate microRNA (miR/miRNA)-34c expression and the association of miR-34c with B cell lymphoma 2 (BCL2) in M4e laryngeal carcinoma cell line. M4e laryngeal carcinoma cells were cultured and transfected with lenti-miR-34c or scramble miRNA for 72 h. Cell viability and the percentage of cells undergoing apoptosis of transfected cells were detected using MTT and Annexin V/allophycocyanin and propidium iodide assays, respectively. Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and western blot analysis were performed to determine BCL2 mRNA and protein expression in transfected M4e cells. In addition, luciferase reporter assay was performed to identify whether BCL2 is a direct target of miR-34c. Transfection of lenti-miR-34c was able to significantly inhibit cell viability (P<0.01), increase the percentage of cells undergoing apoptosis (P<0.001) and downregulate BCL2 protein expression (P<0.01) in M4e cells. RT-qPCR data revealed that lenti-miR-34c transfection did not affect BCL2 mRNA expression. However, data from the luciferase reporter assay revealed that transfection with miR-34c negative control decreased luciferase activity in M4e cells co-transfected with pGL3-BCL2-MUT plasmid, compared with miR-34c inhibitor (P<0.01). Collectively, the results from the present study provided evidence that miR-34c may be involved in the pathogenesis of laryngeal cancer, and BCL2 may be negatively regulated by miR-34c in M4e cells.

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The inhibitory effect of salinomycin on the proliferation, migration and invasion of human endometrial cancer stem-like cells

Cited by 76 publications

References 31 publications

Salinomycin efficiency assessment in non-tumor (HB4a) and tumor (MCF-7) human breast cells

Salinomycin efficiency assessment in non-tumor (HB4a) and tumor (MCF-7) human breast cells

Drug Transporter-Mediated Protection of Cancer Stem Cells From Ionophore Antibiotics

MiR-34c induces apoptosis and inhibits the viability of M4e cells by targeting BCL2

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