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Published in: Molecular Cancer 1/2014

Open Access 01-12-2014 | Short communication

Salinomycin treatment reduces metastatic tumor burden by hampering cancer cell migration

Authors: Florian Kopp, Adam Hermawan, Prajakta Shirish Oak, Annika Herrmann, Ernst Wagner, Andreas Roidl

Published in: Molecular Cancer | Issue 1/2014

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Abstract

Background

Tumor spreading is the major threat for cancer patients. The recently published anti-cancer drug salinomycin raised hope for an improved treatment by targeting therapy-refractory cancer stem cells. However, an unambiguous role of salinomycin against cancer cell migration and metastasis formation remains elusive.

Findings

We report that salinomycin effectively inhibits cancer cell migration in a variety of cancer types as determined by Boyden chamber assays. Additionally, cells were treated with doxorubicin at a concentration causing a comparable low cytotoxicity, emphasizing the anti-migratory potential of salinomycin. Moreover, single-cell tracking by time-lapse microscopy demonstrated a remarkable effect of salinomycin on breast cancer cell motility. Ultimately, salinomycin treatment significantly reduced the metastatic tumor burden in a syngenic mouse tumor model.

Conclusions

Our findings clearly show that salinomycin can strongly inhibit cancer cell migration independent of the induction of cell death. We furthermore demonstrate for the first time that salinomycin treatment reduces metastasis formation in vivo, strengthening its role as promising anti-cancer therapeutic.
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Literature
1.
go back to reference Gupta PB, Onder TT, Jiang G, Tao K, Kuperwasser C, Weinberg RA, Lander ES: Identification of selective inhibitors of cancer stem cells by high-throughput screening. Cell. 2009, 138: 645-659. 10.1016/j.cell.2009.06.034CrossRefPubMed Gupta PB, Onder TT, Jiang G, Tao K, Kuperwasser C, Weinberg RA, Lander ES: Identification of selective inhibitors of cancer stem cells by high-throughput screening. Cell. 2009, 138: 645-659. 10.1016/j.cell.2009.06.034CrossRefPubMed
3.
go back to reference Arafat K, Iratni R, Takahashi T, Parekh K, Al Dhaheri Y, Adrian TE, Attoub S: Inhibitory Effects of Salinomycin on Cell Survival, Colony Growth, Migration, and Invasion of Human Non-Small Cell Lung Cancer A549 and LNM35: Involvement of NAG-1. PLoS One. 2013, 8: e66931- 10.1371/journal.pone.0066931PubMedCentralCrossRefPubMed Arafat K, Iratni R, Takahashi T, Parekh K, Al Dhaheri Y, Adrian TE, Attoub S: Inhibitory Effects of Salinomycin on Cell Survival, Colony Growth, Migration, and Invasion of Human Non-Small Cell Lung Cancer A549 and LNM35: Involvement of NAG-1. PLoS One. 2013, 8: e66931- 10.1371/journal.pone.0066931PubMedCentralCrossRefPubMed
4.
go back to reference Dong TT, Zhou HM, Wang LL, Feng B, Lv B, Zheng MH: Salinomycin selectively targets ‘CD133’+‘ cell subpopulations and decreases malignant traits in colorectal cancer lines. Ann Surg Oncol. 2011, 18: 1797-1804. 10.1245/s10434-011-1561-2CrossRefPubMed Dong TT, Zhou HM, Wang LL, Feng B, Lv B, Zheng MH: Salinomycin selectively targets ‘CD133’+‘ cell subpopulations and decreases malignant traits in colorectal cancer lines. Ann Surg Oncol. 2011, 18: 1797-1804. 10.1245/s10434-011-1561-2CrossRefPubMed
5.
go back to reference He L, Wang F, Dai WQ, Wu D, Lin CL, Wu SM, Cheng P, Zhang Y, Shen M, Wang CF: Mechanism of action of salinomycin on growth and migration in pancreatic cancer cell lines. Pancreatology. 2013, 13: 72-78. 10.1016/j.pan.2012.11.314CrossRefPubMed He L, Wang F, Dai WQ, Wu D, Lin CL, Wu SM, Cheng P, Zhang Y, Shen M, Wang CF: Mechanism of action of salinomycin on growth and migration in pancreatic cancer cell lines. Pancreatology. 2013, 13: 72-78. 10.1016/j.pan.2012.11.314CrossRefPubMed
6.
go back to reference Ketola K, Hilvo M, Hyotylainen T, Vuoristo A, Ruskeepaa AL, Oresic M, Kallioniemi O, Iljin K: Salinomycin inhibits prostate cancer growth and migration via induction of oxidative stress. Br J Cancer. 2012, 106: 99-106. 10.1038/bjc.2011.530PubMedCentralCrossRefPubMed Ketola K, Hilvo M, Hyotylainen T, Vuoristo A, Ruskeepaa AL, Oresic M, Kallioniemi O, Iljin K: Salinomycin inhibits prostate cancer growth and migration via induction of oxidative stress. Br J Cancer. 2012, 106: 99-106. 10.1038/bjc.2011.530PubMedCentralCrossRefPubMed
7.
go back to reference Kusunoki S, Kato K, Tabu K, Inagaki T, Okabe H, Kaneda H, Suga S, Terao Y, Taga T, Takeda S: The inhibitory effect of salinomycin on the proliferation, migration and invasion of human endometrial cancer stem-like cells. Gynecol Oncol. 2013, 129: 598-605. 10.1016/j.ygyno.2013.03.005CrossRefPubMed Kusunoki S, Kato K, Tabu K, Inagaki T, Okabe H, Kaneda H, Suga S, Terao Y, Taga T, Takeda S: The inhibitory effect of salinomycin on the proliferation, migration and invasion of human endometrial cancer stem-like cells. Gynecol Oncol. 2013, 129: 598-605. 10.1016/j.ygyno.2013.03.005CrossRefPubMed
8.
go back to reference Lieke T, Ramackers W, Bergmann S, Klempnauer J, Winkler M, Klose J: Impact of Salinomycin on human cholangiocarcinoma: induction of apoptosis and impairment of tumor cell proliferation in vitro. BMC Cancer. 2012, 12: 466- 10.1186/1471-2407-12-466PubMedCentralCrossRefPubMed Lieke T, Ramackers W, Bergmann S, Klempnauer J, Winkler M, Klose J: Impact of Salinomycin on human cholangiocarcinoma: induction of apoptosis and impairment of tumor cell proliferation in vitro. BMC Cancer. 2012, 12: 466- 10.1186/1471-2407-12-466PubMedCentralCrossRefPubMed
9.
go back to reference Vecsey-Semjen B, Becker KF, Sinski A, Blennow E, Vietor I, Zatloukal K, Beug H, Wagner E, Huber LA: Novel colon cancer cell lines leading to better understanding of the diversity of respective primary cancers. Oncogene. 2002, 21: 4646-4662. 10.1038/sj.onc.1205577CrossRefPubMed Vecsey-Semjen B, Becker KF, Sinski A, Blennow E, Vietor I, Zatloukal K, Beug H, Wagner E, Huber LA: Novel colon cancer cell lines leading to better understanding of the diversity of respective primary cancers. Oncogene. 2002, 21: 4646-4662. 10.1038/sj.onc.1205577CrossRefPubMed
10.
go back to reference Wiedmann RM, von Schwarzenberg K, Palamidessi A, Schreiner L, Kubisch R, Liebl J, Schempp C, Trauner D, Vereb G, Zahler S: The V-ATPase-inhibitor archazolid abrogates tumor metastasis via inhibition of endocytic activation of the Rho-GTPase Rac1. Cancer Res. 2012, 72: 5976-5987. 10.1158/0008-5472.CAN-12-1772CrossRefPubMed Wiedmann RM, von Schwarzenberg K, Palamidessi A, Schreiner L, Kubisch R, Liebl J, Schempp C, Trauner D, Vereb G, Zahler S: The V-ATPase-inhibitor archazolid abrogates tumor metastasis via inhibition of endocytic activation of the Rho-GTPase Rac1. Cancer Res. 2012, 72: 5976-5987. 10.1158/0008-5472.CAN-12-1772CrossRefPubMed
11.
go back to reference Verdoodt B, Vogt M, Schmitz I, Liffers ST, Tannapfel A, Mirmohammadsadegh A: Salinomycin induces autophagy in colon and breast cancer cells with concomitant generation of reactive oxygen species. PLoS One. 2012, 7: e44132- 10.1371/journal.pone.0044132PubMedCentralCrossRefPubMed Verdoodt B, Vogt M, Schmitz I, Liffers ST, Tannapfel A, Mirmohammadsadegh A: Salinomycin induces autophagy in colon and breast cancer cells with concomitant generation of reactive oxygen species. PLoS One. 2012, 7: e44132- 10.1371/journal.pone.0044132PubMedCentralCrossRefPubMed
12.
go back to reference Lan SH, Wu SY, Zuchini R, Lin XZ, Su IJ, Tsai TF, Lin YJ, Wu CT, Liu HS: Autophagy suppresses tumorigenesis of hepatitis B Virus-associated hepatocellular carcinoma through degradation of microRNA-224. Hepatology. 2013, doi:10.1002/hep.26659. [Epub ahead of print] Lan SH, Wu SY, Zuchini R, Lin XZ, Su IJ, Tsai TF, Lin YJ, Wu CT, Liu HS: Autophagy suppresses tumorigenesis of hepatitis B Virus-associated hepatocellular carcinoma through degradation of microRNA-224. Hepatology. 2013, doi:10.1002/hep.26659. [Epub ahead of print]
13.
go back to reference Tuloup-Minguez V, Hamai A, Greffard A, Nicolas V, Codogno P, Botti J: Autophagy modulates cell migration and beta1 integrin membrane recycling. Cell Cycle. 2013, 12: 3317-3328.PubMedCentralCrossRefPubMed Tuloup-Minguez V, Hamai A, Greffard A, Nicolas V, Codogno P, Botti J: Autophagy modulates cell migration and beta1 integrin membrane recycling. Cell Cycle. 2013, 12: 3317-3328.PubMedCentralCrossRefPubMed
14.
15.
go back to reference Wang F, He L, Dai WQ, Xu YP, Wu D, Lin CL, Wu SM, Cheng P, Zhang Y, Shen M: Salinomycin inhibits proliferation and induces apoptosis of human hepatocellular carcinoma cells in vitro and in vivo. PLoS One. 2012, 7: e50638- 10.1371/journal.pone.0050638PubMedCentralCrossRefPubMed Wang F, He L, Dai WQ, Xu YP, Wu D, Lin CL, Wu SM, Cheng P, Zhang Y, Shen M: Salinomycin inhibits proliferation and induces apoptosis of human hepatocellular carcinoma cells in vitro and in vivo. PLoS One. 2012, 7: e50638- 10.1371/journal.pone.0050638PubMedCentralCrossRefPubMed
17.
go back to reference Lee J, Ishihara A, Oxford G, Johnson B, Jacobson K: Regulation of cell movement is mediated by stretch-activated calcium channels. Nature. 1999, 400: 382-386. 10.1038/22578CrossRefPubMed Lee J, Ishihara A, Oxford G, Johnson B, Jacobson K: Regulation of cell movement is mediated by stretch-activated calcium channels. Nature. 1999, 400: 382-386. 10.1038/22578CrossRefPubMed
18.
go back to reference Witze ES, Connacher MK, Houel S, Schwartz MP, Morphew MK, Reid L, Sacks DB, Anseth KS, Ahn NG: Wnt5a directs polarized calcium gradients by recruiting cortical endoplasmic reticulum to the cell trailing edge. Dev Cell. 2013, 26: 645-657. 10.1016/j.devcel.2013.08.019CrossRefPubMed Witze ES, Connacher MK, Houel S, Schwartz MP, Morphew MK, Reid L, Sacks DB, Anseth KS, Ahn NG: Wnt5a directs polarized calcium gradients by recruiting cortical endoplasmic reticulum to the cell trailing edge. Dev Cell. 2013, 26: 645-657. 10.1016/j.devcel.2013.08.019CrossRefPubMed
Metadata
Title
Salinomycin treatment reduces metastatic tumor burden by hampering cancer cell migration
Authors
Florian Kopp
Adam Hermawan
Prajakta Shirish Oak
Annika Herrmann
Ernst Wagner
Andreas Roidl
Publication date
01-12-2014
Publisher
BioMed Central
Published in
Molecular Cancer / Issue 1/2014
Electronic ISSN: 1476-4598
DOI
https://doi.org/10.1186/1476-4598-13-16

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