Salinomycin inhibits prostate cancer growth and migration via induction of oxidative stress

Ketola, Kirsi; Hilvo, Mika; Hyötyläinen, Tuulia; Vuoristo, Anu; Ruskeepää, Anna Liisa; Orešič, Matej; Kallioniemi, Olli; Iljin, Kristiina

doi:10.1038/bjc.2011.530

Cited by 145 publications

(118 citation statements)

References 61 publications

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“…It has recently been reported that salinomycin can selectively kill human breast cancer stem cells, and is 100-fold more effective at reducing the proportion of CSCs than paclitaxel, albeit by an unknown mechanism (19). Salinomycin was also found to be a selective inhibitor of human lung, gastric, osteosarcoma, squamous cell carcinoma, prostate and pancreatic CSCs (20)(21)(22)(23)(24)(25). However, since the mechanism involved in the salinomycin anti-CSC activity is poorly understood, it is necessary to conduct more in-depth research into the activity of salinomycin in different types of human CSCs.…”

Section: Introductionmentioning

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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Section: Introductionmentioning

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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“…Additionally, it was reported that Salinomycin induces apoptosis in prostate cancer cells via accumulation of reactive oxygen species and mitochondrial membrane depolarization [39]. Furthermore, Salinomycin inhibits prostate cancer growth via reduction of the expression of key oncogenes and induction of oxidative stress in cultured prostate cancer cells [32]. Taken together, several mechanisms are supposed to be responsible for the effects of Salinomycin to human cancer cells, which have to be investigated in greater detail in the near future.…”

Section: Discussionmentioning

confidence: 99%

“…Exposure of Salinomycin to Mz-ChA-1 and TFK-1 cells, which were both originally isolated from an extrahepatic bile duct carcinoma [21,22], resulted in a high percentage of apoptotic tumor cells, while EGI-1 cells seem to be less susceptible for treatment with Salinomycin even after treatment with high concentrations. It has been reported that Salinomycin selectively affects malignant cells whereas non-malignant cells do not undergo apoptosis after treatment with Salinomycin [20,31,32]. Given that EGI-1 cells are originally isolated from a poorly differentiated human bile duct adenocarcinoma [23] and therewith undoubted are malignant, it remains unclear why these cells are nearly apoptosis-resistant to treatment with Salinomycin.…”

Section: Discussionmentioning

confidence: 99%

Impact of Salinomycin on human cholangiocarcinoma: induction of apoptosis and impairment of tumor cell proliferation in vitro

Lieke¹,

Ramackers²,

Bergmann³

et al. 2013

Z Gastroenterol

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Background: Cholangiocarcinoma (CC) is a primary liver cancer with increasing incidence worldwide. Despite all efforts made in past years, prognosis remains to be poor. At least in part, this might be explained by a pronounced resistance of CC cells to undergo apoptosis. Thus, new therapeutic strategies are imperatively required. In this study we investigated the effect of Salinomycin, a polyether ionophore antibiotic, on CC cells as an appropriate agent to treat CC. Salinomycin was quite recently identified to induce apoptosis in cancer stem cells and to overcome apoptosis-resistance in several leukemia-cells and other cancer cell lines of different origin. Methods: To delineate the effects of Salinomycin on CC, we established an in vitro cell culture model using three different human CC cell lines. After treatment apoptosis as well as migration and proliferation behavior was assessed and additional cell cycle analyses were performed by flowcytometry.

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“…Blockade of the SHH signaling pathway, which is important in stem cell self-renewal, by cyclopamine leads to long-term PC regression without recurrence, strongly suggesting a connection between this pathway and PCSCs [121]. Salinomycin, a structurally related compound to monensin, was recently identified as a potent PCSC inhibitor [122]. It inhibited the growth of PCs, but did not affect non-malignant prostate epithelial cells.…”

Section: New Therapeutic Approaches In Targeting Pcscsmentioning

confidence: 99%

Stem Cells and Prostate Cancer

Çetintaş¹,

Kaymaz²,

Kosova³

2013

Advances in Prostate Cancer

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Salinomycin inhibits prostate cancer growth and migration via induction of oxidative stress

Cited by 145 publications

References 61 publications

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

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

Impact of Salinomycin on human cholangiocarcinoma: induction of apoptosis and impairment of tumor cell proliferation in vitro

Stem Cells and Prostate Cancer

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