Monensin Induced Oxidative Stress Reduces Prostate Cancer Cell Migration and Cancer Stem Cell Population

Ketola, Kirsi; Vuoristo, Anu; Orešič, Matej; Kallioniemi, Olli; Iljin, Kristiina

doi:10.5772/34713

Cited by 3 publications

(3 citation statements)

References 82 publications

(89 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…E-cadherin is commonly known marker for cancer cell differentiation and it is downregulated in invasive prostatic carcinoma [26]. We have previously shown that induction of E-cadherin expression is associated with reduced cell proliferation in ERG positive VCaP prostate cancer cells [27], [28]. These results indicate that morphological phenotype seen in response to sunitinib-disulfiram cotreatment correlates with elevated E-cadherin expression in VCaP prostate cancer cells.…”

Section: Resultsmentioning

confidence: 65%

Chemical Biology Drug Sensitivity Screen Identifies Sunitinib as Synergistic Agent with Disulfiram in Prostate Cancer Cells

2012

Self Cite

View full text Add to dashboard Cite

BackgroundCurrent treatment options for castration- and treatment-resistant prostate cancer are limited and novel approaches are desperately needed. Our recent results from a systematic chemical biology sensitivity screen covering most known drugs and drug-like molecules indicated that aldehyde dehydrogenase inhibitor disulfiram is one of the most potent cancer-specific inhibitors of prostate cancer cell growth, including TMPRSS2-ERG fusion positive cancers. However, the results revealed that disulfiram alone does not block tumor growth in vivo nor induce apoptosis in vitro, indicating that combinatorial approaches may be required to enhance the anti-neoplastic effects.Methods and FindingsIn this study, we utilized a chemical biology drug sensitivity screen to explore disulfiram mechanistic details and to identify compounds potentiating the effect of disulfiram in TMPRSS2-ERG fusion positive prostate cancer cells. In total, 3357 compounds including current chemotherapeutic agents as well as drug-like small molecular compounds were screened alone and in combination with disulfiram. Interestingly, the results indicated that androgenic and antioxidative compounds antagonized disulfiram effect whereas inhibitors of receptor tyrosine kinase, proteasome, topoisomerase II, glucosylceramide synthase or cell cycle were among compounds sensitizing prostate cancer cells to disulfiram. The combination of disulfiram and an antiangiogenic agent sunitinib was studied in more detail, since both are already in clinical use in humans. Disulfiram-sunitinib combination induced apoptosis and reduced androgen receptor protein expression more than either of the compounds alone. Moreover, combinatorial exposure reduced metastatic characteristics such as cell migration and 3D cell invasion as well as induced epithelial differentiation shown as elevated E-cadherin expression.ConclusionsTaken together, our results propose novel combinatorial approaches to inhibit prostate cancer cell growth. Disulfiram-sunitinib combination was identified as one of the potent synergistic approaches. Since sunitinib alone has been reported to lack efficacy in prostate cancer clinical trials, our results provide a rationale for novel combinatorial approach to target prostate cancer more efficiently.

show abstract

Section: Resultsmentioning

confidence: 65%

Chemical Biology Drug Sensitivity Screen Identifies Sunitinib as Synergistic Agent with Disulfiram in Prostate Cancer Cells

2012

Self Cite

View full text Add to dashboard Cite

show abstract

“…Later Ketola et al and Kim et al reported on the ability of Monensin to elevate intracellular oxidative stress in prostate cancer cells by increasing the generation of intracellular reactive oxygen species and by induction of a transcriptional profile characteristic of an oxidative stress response [20][21][22]. The observed effects were potentiated by combinatorial treatment with antiandrogens and antagonized by antioxidant vitamin C.…”

Section: Introductionmentioning

confidence: 99%

Study on in vitro Toxicity of Biometal(II) Monensinates Against Rat Zajdela Liver Tumour

Alexandrova

Zhivkova

Ivanov

et al. 2020

Chemistry-Didactics-Ecology-Metrology

View full text Add to dashboard Cite

The ability of Monensic acid A (MonH∙H2O) and its neutral metal complexes [M(Mon)2(H2O)2]with ions of Mg2+, Ca2+, Mn2+, Co2+, Ni2+ and Zn2+ to decrease viability and proliferation of primary cell cultures, originating from a chemically induced transplantable liver tumour of Zajdela in rats, and bone marrow cells from the same tumour-bearers, was evaluated. Experimental data revealed that manganese(II) and nickel(II) complexes of Monensin A are relatively more selective against the tumour as compared to the healthy bone marrow cells.

show abstract

“…In this study, salinomycin was reported to reduce the proportion of CSCs by greater than 100-fold relative to the chemotherapy drug paclitaxel, and such preferential killing of drug-resistant and stem-like tumor cells has subsequently been shown in several malignancies (reviewed in (Naujokat & Steinhart, 2012)). Other ionophores have also been reported to impact cells with mesenchymal attributes; the polyether ionophores nigericin (Gupta et al , 2009) and monensin (Ketola et al, 2012; Shaik et al, 2004) have been reported to selectively kill stem-like tumor cells or to reduce drug-resistance and stemness markers, respectively, and the channel-forming ionophore gramicidin A was shown to inhibit hypoxia-inducible factor (HIF) (David et al, 2014), a well-known driver of mesenchymalization in solid tumors (Haase, 2009). …”

Section: Direct Targeting Of Mesenchymalized Tumor Cellsmentioning

confidence: 99%

Pharmacological and immunological targeting of tumor mesenchymalization

David

Dominguez

Palena

2017

Pharmacology & Therapeutics

View full text Add to dashboard Cite

Controlling the spread of carcinoma cells to distant organs is the foremost challenge in cancer treatment, as metastatic disease is generally resistant to therapy and is ultimately incurable for the majority of patients. The plasticity of tumor cell phenotype, in which the behaviors and functions of individual tumor cells differ markedly depending upon intrinsic and extrinsic factors, is now known to be a central mechanism in cancer progression. Our expanding knowledge of epithelial and mesenchymal phenotypic states in tumor cells, and the dynamic nature of the transitions between these phenotypes has created new opportunities to intervene to better control the behavior of tumor cells. There are now a variety of innovative pharmacological approaches to preferentially target tumor cells that have acquired mesenchymal features, including cytotoxic agents that directly kill these cells, and inhibitors that block or revert the process of mesenchymalization. Furthermore, novel immunological strategies have been developed to engage the immune system in seeking out and destroying mesenchymalized tumor cells. This review highlights the relevance of phenotypic plasticity in tumor biology, and discusses recently developed pharmacological and immunological means of targeting this phenomenon.

show abstract

Monensin Induced Oxidative Stress Reduces Prostate Cancer Cell Migration and Cancer Stem Cell Population

Cited by 3 publications

References 82 publications

Chemical Biology Drug Sensitivity Screen Identifies Sunitinib as Synergistic Agent with Disulfiram in Prostate Cancer Cells

Chemical Biology Drug Sensitivity Screen Identifies Sunitinib as Synergistic Agent with Disulfiram in Prostate Cancer Cells

Study on in vitro Toxicity of Biometal(II) Monensinates Against Rat Zajdela Liver Tumour

Pharmacological and immunological targeting of tumor mesenchymalization

Contact Info

Product

Resources

About