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

Kirsi Ketola, Mika Hilvo, Tuulia Hyötyläinen, A. Vuoristo, Anna-Liisa Ruskeepää, Matej Orešič, Olli Kallioniemi, Kristiina Iljin (Corresponding Author)

Research output: Contribution to journalArticleScientificpeer-review

108 Citations (Scopus)

Abstract

Background:

We have shown that a sodium ionophore monensin inhibits prostate cancer cell growth. A structurally related compound to monensin, salinomycin, was recently identified as a putative cancer stem cell inhibitor.

Methods:

The growth inhibitory potential of salinomycin was studied in a panel of prostate cells. To get insights into the mechanism of action, a variety of assays such as gene expression and steroid profiling were performed in salinomycin-exposed prostate cancer cells.

Results:

Salinomycin inhibited the growth of prostate cancer cells, but did not affect non-malignant prostate epithelial cells. Salinomycin impacted on prostate cancer stem cell functions as evidenced by reduced aldehyde dehydrogenase activity and the fraction of CD44+ cells. Moreover, salinomycin reduced the expression of MYC, AR and ERG, induced oxidative stress as well as inhibited nuclear factor-κB activity and cell migration. Furthermore, profiling steroid metabolites revealed increased levels of oxidative stress-inducing steroids 7-ketocholesterol and aldosterone and decreased levels of antioxidative steroids progesterone and pregnenolone in salinomycin-exposed prostate cancer cells.

Conclusion:

Our results indicate that salinomycin inhibits prostate cancer cell growth and migration by reducing the expression of key prostate cancer oncogenes, inducing oxidative stress, decreasing the antioxidative capacity and cancer stem cell fraction.

Original languageEnglish
Pages (from-to)99-106
Number of pages8
JournalBritish Journal of Cancer
Volume106
Issue number1
DOIs
Publication statusPublished - 2012
MoE publication typeA1 Journal article-refereed

Fingerprint

Prostatic Neoplasms
Oxidative Stress
Growth
Neoplastic Stem Cells
Steroids
Monensin
Cell Movement
Prostate
Sodium Ionophores
Pregnenolone
Aldehyde Dehydrogenase
salinomycin
Gene Expression Profiling
Aldosterone
Oncogenes
Progesterone
Epithelial Cells

Keywords

  • salinomycin
  • prostate cancer
  • oxidative stress
  • cancer stem cells

Cite this

Ketola, Kirsi ; Hilvo, Mika ; Hyötyläinen, Tuulia ; Vuoristo, A. ; Ruskeepää, Anna-Liisa ; Orešič, Matej ; Kallioniemi, Olli ; Iljin, Kristiina. / Salinomycin inhibits prostate cancer growth and migration via induction of oxidative stress. In: British Journal of Cancer. 2012 ; Vol. 106, No. 1. pp. 99-106.
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abstract = "Background:We have shown that a sodium ionophore monensin inhibits prostate cancer cell growth. A structurally related compound to monensin, salinomycin, was recently identified as a putative cancer stem cell inhibitor.Methods:The growth inhibitory potential of salinomycin was studied in a panel of prostate cells. To get insights into the mechanism of action, a variety of assays such as gene expression and steroid profiling were performed in salinomycin-exposed prostate cancer cells.Results:Salinomycin inhibited the growth of prostate cancer cells, but did not affect non-malignant prostate epithelial cells. Salinomycin impacted on prostate cancer stem cell functions as evidenced by reduced aldehyde dehydrogenase activity and the fraction of CD44+ cells. Moreover, salinomycin reduced the expression of MYC, AR and ERG, induced oxidative stress as well as inhibited nuclear factor-κB activity and cell migration. Furthermore, profiling steroid metabolites revealed increased levels of oxidative stress-inducing steroids 7-ketocholesterol and aldosterone and decreased levels of antioxidative steroids progesterone and pregnenolone in salinomycin-exposed prostate cancer cells.Conclusion:Our results indicate that salinomycin inhibits prostate cancer cell growth and migration by reducing the expression of key prostate cancer oncogenes, inducing oxidative stress, decreasing the antioxidative capacity and cancer stem cell fraction.",
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Ketola, K, Hilvo, M, Hyötyläinen, T, Vuoristo, A, Ruskeepää, A-L, Orešič, M, Kallioniemi, O & Iljin, K 2012, 'Salinomycin inhibits prostate cancer growth and migration via induction of oxidative stress', British Journal of Cancer, vol. 106, no. 1, pp. 99-106. https://doi.org/10.1038/bjc.2011.530

Salinomycin inhibits prostate cancer growth and migration via induction of oxidative stress. / Ketola, Kirsi; Hilvo, Mika; Hyötyläinen, Tuulia; Vuoristo, A.; Ruskeepää, Anna-Liisa; Orešič, Matej; Kallioniemi, Olli; Iljin, Kristiina (Corresponding Author).

In: British Journal of Cancer, Vol. 106, No. 1, 2012, p. 99-106.

Research output: Contribution to journalArticleScientificpeer-review

TY - JOUR

T1 - Salinomycin inhibits prostate cancer growth and migration via induction of oxidative stress

AU - Ketola, Kirsi

AU - Hilvo, Mika

AU - Hyötyläinen, Tuulia

AU - Vuoristo, A.

AU - Ruskeepää, Anna-Liisa

AU - Orešič, Matej

AU - Kallioniemi, Olli

AU - Iljin, Kristiina

PY - 2012

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N2 - Background:We have shown that a sodium ionophore monensin inhibits prostate cancer cell growth. A structurally related compound to monensin, salinomycin, was recently identified as a putative cancer stem cell inhibitor.Methods:The growth inhibitory potential of salinomycin was studied in a panel of prostate cells. To get insights into the mechanism of action, a variety of assays such as gene expression and steroid profiling were performed in salinomycin-exposed prostate cancer cells.Results:Salinomycin inhibited the growth of prostate cancer cells, but did not affect non-malignant prostate epithelial cells. Salinomycin impacted on prostate cancer stem cell functions as evidenced by reduced aldehyde dehydrogenase activity and the fraction of CD44+ cells. Moreover, salinomycin reduced the expression of MYC, AR and ERG, induced oxidative stress as well as inhibited nuclear factor-κB activity and cell migration. Furthermore, profiling steroid metabolites revealed increased levels of oxidative stress-inducing steroids 7-ketocholesterol and aldosterone and decreased levels of antioxidative steroids progesterone and pregnenolone in salinomycin-exposed prostate cancer cells.Conclusion:Our results indicate that salinomycin inhibits prostate cancer cell growth and migration by reducing the expression of key prostate cancer oncogenes, inducing oxidative stress, decreasing the antioxidative capacity and cancer stem cell fraction.

AB - Background:We have shown that a sodium ionophore monensin inhibits prostate cancer cell growth. A structurally related compound to monensin, salinomycin, was recently identified as a putative cancer stem cell inhibitor.Methods:The growth inhibitory potential of salinomycin was studied in a panel of prostate cells. To get insights into the mechanism of action, a variety of assays such as gene expression and steroid profiling were performed in salinomycin-exposed prostate cancer cells.Results:Salinomycin inhibited the growth of prostate cancer cells, but did not affect non-malignant prostate epithelial cells. Salinomycin impacted on prostate cancer stem cell functions as evidenced by reduced aldehyde dehydrogenase activity and the fraction of CD44+ cells. Moreover, salinomycin reduced the expression of MYC, AR and ERG, induced oxidative stress as well as inhibited nuclear factor-κB activity and cell migration. Furthermore, profiling steroid metabolites revealed increased levels of oxidative stress-inducing steroids 7-ketocholesterol and aldosterone and decreased levels of antioxidative steroids progesterone and pregnenolone in salinomycin-exposed prostate cancer cells.Conclusion:Our results indicate that salinomycin inhibits prostate cancer cell growth and migration by reducing the expression of key prostate cancer oncogenes, inducing oxidative stress, decreasing the antioxidative capacity and cancer stem cell fraction.

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KW - prostate cancer

KW - oxidative stress

KW - cancer stem cells

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JO - British Journal of Cancer

JF - British Journal of Cancer

SN - 0007-0920

IS - 1

ER -