Repurposing atovaquone: targeting mitochondrial complex III and OXPHOS to eradicate cancer stem cells

Atovaquone is an FDA-approved anti-malarial drug, which first became clinically available in the year 2000. Currently, its main usage is for the treatment of pneumocystis pneumonia (PCP) and/or toxoplasmosis in immune-compromised patients. Atovaquone is a hydroxy-1,4-naphthoquinone analogue of ubiqu...

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Veröffentlicht in:Oncotarget Jg. 7; H. 23; S. 34084 - 34099
Hauptverfasser: Fiorillo, Marco, Lamb, Rebecca, Tanowitz, Herbert B, Mutti, Luciano, Krstic-Demonacos, Marija, Cappello, Anna Rita, Martinez-Outschoorn, Ubaldo E, Sotgia, Federica, Lisanti, Michael P
Format: Journal Article
Sprache:Englisch
Veröffentlicht: United States 07.06.2016
Schlagworte:
Antimalarials - pharmacology
Antineoplastic Agents - pharmacology
Atovaquone - pharmacology
Drug Repositioning
Electron Transport Complex III - antagonists & inhibitors
Humans
MCF-7 Cells
Neoplastic Stem Cells - drug effects
Oxidative Phosphorylation - drug effects
tumor-initiating cells (TICs)
OXPHOS
cancer stem-like cells (CSCs)
atovaquone
mitochondria
ISSN:1949-2553
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Abstract Atovaquone is an FDA-approved anti-malarial drug, which first became clinically available in the year 2000. Currently, its main usage is for the treatment of pneumocystis pneumonia (PCP) and/or toxoplasmosis in immune-compromised patients. Atovaquone is a hydroxy-1,4-naphthoquinone analogue of ubiquinone, also known as Co-enzyme Q10 (CoQ10). It is a well-tolerated drug that does not cause myelo-suppression. Mechanistically, it is thought to act as a potent and selective OXPHOS inhibitor, by targeting the CoQ10-dependence of mitochondrial complex III. Here, we show for the first time that atovaquone also has anti-cancer activity, directed against Cancer Stem-like Cells (CSCs). More specifically, we demonstrate that atovaquone treatment of MCF7 breast cancer cells inhibits oxygen-consumption and metabolically induces aerobic glycolysis (the Warburg effect), as well as oxidative stress. Remarkably, atovaquone potently inhibits the propagation of MCF7-derived CSCs, with an IC-50 of 1 μM, as measured using the mammosphere assay. Atovaquone also maintains this selectivity and potency in mixed populations of CSCs and non-CSCs. Importantly, these results indicate that glycolysis itself is not sufficient to maintain the proliferation of CSCs, which is instead strictly dependent on mitochondrial function. In addition to targeting the proliferation of CSCs, atovaquone also induces apoptosis in both CD44+/CD24low/- CSC and ALDH+ CSC populations, during exposure to anchorage-independent conditions for 12 hours. However, it has no effect on oxygen consumption in normal human fibroblasts and, in this cellular context, behaves as an anti-inflammatory, consistent with the fact that it is well-tolerated in patients treated for infections. Future studies in xenograft models and human clinical trials may be warranted, as the IC-50 of atovaquone's action on CSCs (1 μM) is >50 times less than its average serum concentration in humans.
AbstractList Atovaquone is an FDA-approved anti-malarial drug, which first became clinically available in the year 2000. Currently, its main usage is for the treatment of pneumocystis pneumonia (PCP) and/or toxoplasmosis in immune-compromised patients. Atovaquone is a hydroxy-1,4-naphthoquinone analogue of ubiquinone, also known as Co-enzyme Q10 (CoQ10). It is a well-tolerated drug that does not cause myelo-suppression. Mechanistically, it is thought to act as a potent and selective OXPHOS inhibitor, by targeting the CoQ10-dependence of mitochondrial complex III. Here, we show for the first time that atovaquone also has anti-cancer activity, directed against Cancer Stem-like Cells (CSCs). More specifically, we demonstrate that atovaquone treatment of MCF7 breast cancer cells inhibits oxygen-consumption and metabolically induces aerobic glycolysis (the Warburg effect), as well as oxidative stress. Remarkably, atovaquone potently inhibits the propagation of MCF7-derived CSCs, with an IC-50 of 1 μM, as measured using the mammosphere assay. Atovaquone also maintains this selectivity and potency in mixed populations of CSCs and non-CSCs. Importantly, these results indicate that glycolysis itself is not sufficient to maintain the proliferation of CSCs, which is instead strictly dependent on mitochondrial function. In addition to targeting the proliferation of CSCs, atovaquone also induces apoptosis in both CD44+/CD24low/- CSC and ALDH+ CSC populations, during exposure to anchorage-independent conditions for 12 hours. However, it has no effect on oxygen consumption in normal human fibroblasts and, in this cellular context, behaves as an anti-inflammatory, consistent with the fact that it is well-tolerated in patients treated for infections. Future studies in xenograft models and human clinical trials may be warranted, as the IC-50 of atovaquone's action on CSCs (1 μM) is >50 times less than its average serum concentration in humans.
Author Tanowitz, Herbert B
Cappello, Anna Rita
Krstic-Demonacos, Marija
Lamb, Rebecca
Sotgia, Federica
Lisanti, Michael P
Mutti, Luciano
Martinez-Outschoorn, Ubaldo E
Fiorillo, Marco
Author_xml – sequence: 1
  givenname: Marco
  surname: Fiorillo
  fullname: Fiorillo, Marco
  organization: The Department of Pharmacy, Health and Nutritional Sciences, The University of Calabria, Cosenza, Italy
– sequence: 2
  givenname: Rebecca
  surname: Lamb
  fullname: Lamb, Rebecca
  organization: The Breast Cancer Now Research Unit, Institute of Cancer Sciences, Cancer Research UK Manchester Institute, University of Manchester, Manchester, UK
– sequence: 3
  givenname: Herbert B
  surname: Tanowitz
  fullname: Tanowitz, Herbert B
  organization: Department of Medicine and Pathology, Albert Einstein College of Medicine, Bronx, NY, USA
– sequence: 4
  givenname: Luciano
  surname: Mutti
  fullname: Mutti, Luciano
  organization: School of Environment and Life Sciences, University of Salford, Salford, UK
– sequence: 5
  givenname: Marija
  surname: Krstic-Demonacos
  fullname: Krstic-Demonacos, Marija
  organization: School of Environment and Life Sciences, University of Salford, Salford, UK
– sequence: 6
  givenname: Anna Rita
  surname: Cappello
  fullname: Cappello, Anna Rita
  organization: The Department of Pharmacy, Health and Nutritional Sciences, The University of Calabria, Cosenza, Italy
– sequence: 7
  givenname: Ubaldo E
  surname: Martinez-Outschoorn
  fullname: Martinez-Outschoorn, Ubaldo E
  organization: The Sidney Kimmel Cancer Center, Philadelphia, PA, USA
– sequence: 8
  givenname: Federica
  surname: Sotgia
  fullname: Sotgia, Federica
  organization: The Manchester Centre for Cellular Metabolism (MCCM), Institute of Cancer Sciences, Cancer Research UK Manchester Institute, University of Manchester, Manchester, UK
– sequence: 9
  givenname: Michael P
  surname: Lisanti
  fullname: Lisanti, Michael P
  organization: The Manchester Centre for Cellular Metabolism (MCCM), Institute of Cancer Sciences, Cancer Research UK Manchester Institute, University of Manchester, Manchester, UK
BackLink https://www.ncbi.nlm.nih.gov/pubmed/27136895$$D View this record in MEDLINE/PubMed
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Issue 23
Keywords tumor-initiating cells (TICs)
OXPHOS
cancer stem-like cells (CSCs)
atovaquone
mitochondria
Language English
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References 22428931 - Photochem Photobiol. 2012 Jul-Aug;88(4):1016-22
25244355 - J Med Chem. 2014 Oct 9;57(19):7990-8
24905005 - Mol Cell. 2014 Jun 5;54(5):716-27
11101003 - Cell Biol Toxicol. 2000;16(4):207-19
15047214 - Gynecol Oncol. 2004 Apr;93(1):54-8
22665270 - J Mammary Gland Biol Neoplasia. 2012 Jun;17(2):111-7
21215626 - Bioorg Med Chem Lett. 2011 Feb 1;21(3):1052-6
25850553 - Nat Rev Clin Oncol. 2015 Aug;12(8):445-64
18245469 - Cancer Res. 2008 Feb 1;68(3):700-6
17222787 - Cancer Cell. 2007 Jan;11(1):3-5
21389643 - J Nippon Med Sch. 2011;78(1):13-21
9020100 - J Biol Chem. 1997 Feb 14;272(7):3961-6
19632833 - Bioorg Med Chem Lett. 2009 Sep 1;19(17):5091-4
26087310 - Oncotarget. 2015 Jun 20;6(17 ):14777-95
25708684 - Oncotarget. 2015 Feb 28;6(6):3553-62
19169242 - Nature. 2009 Apr 9;458(7239):776-9
26492365 - Cell Death Dis. 2015 Oct 22;6:e1930
15917236 - J Biol Chem. 2005 Jul 22;280(29):27458-65
10610011 - Pharmacotherapy. 1999 Sep;19(9):1050-6
18366788 - Breast Cancer Res. 2008;10(2):R25
8479489 - N Engl J Med. 1993 May 27;328(21):1521-7
20530697 - Clin Cancer Res. 2010 Jun 15;16(12):3153-62
23208510 - Oncogene. 2013 Jul 25;32(30):3483-90
8684102 - Lancet. 1996 Jun 1;347(9014):1511-4
21172432 - Biochim Biophys Acta. 2011 Aug;1812(8):1032-40
26406445 - PLoS One. 2015 Sep 25;10(9):e0136192
25625193 - Oncotarget. 2015 Mar 10;6(7):4569-84
16377171 - Curr Opin Genet Dev. 2006 Feb;16(1):60-4
25562155 - Cell Physiol Biochem. 2014;34(6):2070-80
15108804 - Curr Opin Genet Dev. 2004 Feb;14(1):43-7
15207251 - Crit Rev Oncol Hematol. 2004 Jul;51(1):1-28
25415228 - Oncotarget. 2014 Nov 30;5(22):11029-37
19545218 - Expert Opin Biol Ther. 2009 Aug;9(8):1005-16
10447880 - Mol Microbiol. 1999 Aug;33(4):704-11
9806551 - Nat Genet. 1998 Nov;20(3):291-3
19682730 - Cell. 2009 Aug 21;138(4):645-59
19569044 - Int J Cancer. 2009 Dec 15;125(12):2829-35
26365176 - Cell Metab. 2015 Oct 6;22(4):590-605
1314606 - Biochem Pharmacol. 1992 Apr 1;43(7):1545-53
23903006 - J Pharmacol Sci. 2013;122(4):299-304
17899367 - Breast Cancer Res Treat. 2008 Aug;110(3):439-52
22094260 - Cancer Cell. 2011 Nov 15;20(5):674-88
20531305 - Oncogene. 2010 Aug 26;29(34):4741-51
18445819 - J Natl Cancer Inst. 2008 May 7;100(9):672-9
25915429 - Oncotarget. 2015 May 10;6(13):10728-45
16810242 - Nature. 2006 Jun 29;441(7097):1075-9
References_xml – reference: 17899367 - Breast Cancer Res Treat. 2008 Aug;110(3):439-52
– reference: 25708684 - Oncotarget. 2015 Feb 28;6(6):3553-62
– reference: 26365176 - Cell Metab. 2015 Oct 6;22(4):590-605
– reference: 20530697 - Clin Cancer Res. 2010 Jun 15;16(12):3153-62
– reference: 1314606 - Biochem Pharmacol. 1992 Apr 1;43(7):1545-53
– reference: 10610011 - Pharmacotherapy. 1999 Sep;19(9):1050-6
– reference: 17222787 - Cancer Cell. 2007 Jan;11(1):3-5
– reference: 19545218 - Expert Opin Biol Ther. 2009 Aug;9(8):1005-16
– reference: 25244355 - J Med Chem. 2014 Oct 9;57(19):7990-8
– reference: 21172432 - Biochim Biophys Acta. 2011 Aug;1812(8):1032-40
– reference: 16810242 - Nature. 2006 Jun 29;441(7097):1075-9
– reference: 19632833 - Bioorg Med Chem Lett. 2009 Sep 1;19(17):5091-4
– reference: 19569044 - Int J Cancer. 2009 Dec 15;125(12):2829-35
– reference: 26087310 - Oncotarget. 2015 Jun 20;6(17 ):14777-95
– reference: 25625193 - Oncotarget. 2015 Mar 10;6(7):4569-84
– reference: 9020100 - J Biol Chem. 1997 Feb 14;272(7):3961-6
– reference: 23903006 - J Pharmacol Sci. 2013;122(4):299-304
– reference: 16377171 - Curr Opin Genet Dev. 2006 Feb;16(1):60-4
– reference: 19169242 - Nature. 2009 Apr 9;458(7239):776-9
– reference: 8684102 - Lancet. 1996 Jun 1;347(9014):1511-4
– reference: 15917236 - J Biol Chem. 2005 Jul 22;280(29):27458-65
– reference: 25915429 - Oncotarget. 2015 May 10;6(13):10728-45
– reference: 21389643 - J Nippon Med Sch. 2011;78(1):13-21
– reference: 18245469 - Cancer Res. 2008 Feb 1;68(3):700-6
– reference: 26406445 - PLoS One. 2015 Sep 25;10(9):e0136192
– reference: 25850553 - Nat Rev Clin Oncol. 2015 Aug;12(8):445-64
– reference: 15108804 - Curr Opin Genet Dev. 2004 Feb;14(1):43-7
– reference: 24905005 - Mol Cell. 2014 Jun 5;54(5):716-27
– reference: 20531305 - Oncogene. 2010 Aug 26;29(34):4741-51
– reference: 22428931 - Photochem Photobiol. 2012 Jul-Aug;88(4):1016-22
– reference: 8479489 - N Engl J Med. 1993 May 27;328(21):1521-7
– reference: 22094260 - Cancer Cell. 2011 Nov 15;20(5):674-88
– reference: 15207251 - Crit Rev Oncol Hematol. 2004 Jul;51(1):1-28
– reference: 22665270 - J Mammary Gland Biol Neoplasia. 2012 Jun;17(2):111-7
– reference: 21215626 - Bioorg Med Chem Lett. 2011 Feb 1;21(3):1052-6
– reference: 11101003 - Cell Biol Toxicol. 2000;16(4):207-19
– reference: 19682730 - Cell. 2009 Aug 21;138(4):645-59
– reference: 18366788 - Breast Cancer Res. 2008;10(2):R25
– reference: 10447880 - Mol Microbiol. 1999 Aug;33(4):704-11
– reference: 9806551 - Nat Genet. 1998 Nov;20(3):291-3
– reference: 25415228 - Oncotarget. 2014 Nov 30;5(22):11029-37
– reference: 25562155 - Cell Physiol Biochem. 2014;34(6):2070-80
– reference: 18445819 - J Natl Cancer Inst. 2008 May 7;100(9):672-9
– reference: 15047214 - Gynecol Oncol. 2004 Apr;93(1):54-8
– reference: 26492365 - Cell Death Dis. 2015 Oct 22;6:e1930
– reference: 23208510 - Oncogene. 2013 Jul 25;32(30):3483-90
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Snippet Atovaquone is an FDA-approved anti-malarial drug, which first became clinically available in the year 2000. Currently, its main usage is for the treatment of...
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SubjectTerms Antimalarials - pharmacology
Antineoplastic Agents - pharmacology
Atovaquone - pharmacology
Drug Repositioning
Electron Transport Complex III - antagonists & inhibitors
Humans
MCF-7 Cells
Neoplastic Stem Cells - drug effects
Oxidative Phosphorylation - drug effects
Title Repurposing atovaquone: targeting mitochondrial complex III and OXPHOS to eradicate cancer stem cells
URI https://www.ncbi.nlm.nih.gov/pubmed/27136895
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