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Pharmacol Res Perspect. 2015 Aug;3(4):e00154. doi: 10.1002/prp2.154. Epub 2015 Jun 24.

Efficacy of tomato concentrates in mouse models of dyslipidemia and cancer.

Pharmacology research & perspectives

Arnab Chattopadhyay, Victor Grijalva, Greg Hough, Feng Su, Pallavi Mukherjee, Robin Farias-Eisner, G M Anantharamaiah, Kym F Faull, Lin H Hwang, Mohamad Navab, Alan M Fogelman, Srinivasa T Reddy

Affiliations

  1. Division of Cardiology, Department of Medicine, David Geffen School of Medicine at UCLA Los Angeles, California, 90095-1736.
  2. Department of Obstetrics and Gynecology, David Geffen School of Medicine at UCLA Los Angeles, California, 90095-1736.
  3. Department of Medicine, University of Alabama at Birmingham Birmingham, Alabama, 35294.
  4. Semel Institute for Neuroscience and Human Behavior, David Geffen School of Medicine at UCLA Los Angeles, California, 90095-1736.
  5. Division of Cardiology, Department of Medicine, David Geffen School of Medicine at UCLA Los Angeles, California, 90095-1736 ; Department of Obstetrics and Gynecology, David Geffen School of Medicine at UCLA Los Angeles, California, 90095-1736 ; Department of Molecular and Medical Pharmacology, David Geffen School of Medicine at UCLA Los Angeles, California, 90095-1736.

PMID: 26171234 PMCID: PMC4492730 DOI: 10.1002/prp2.154

Abstract

We previously reported that adding freeze-dried tomato powder from transgenic plants expressing the apolipoprotein A-I mimetic peptide 6F at 2.2% by weight to a Western diet (WD) ameliorated dyslipidemia and atherosclerosis in mice. The same dose in a human would require three cups of tomato powder three times daily. To reduce the volume, we sought a method to concentrate 6F. Remarkably, extracting the transgenic freeze-dried tomato overnight in ethyl acetate with 5% acetic acid resulted in a 37-fold reduction in the amount of transgenic tomato needed for biologic activity. In a mouse model of dyslipidemia, adding 0.06% by weight of the tomato concentrate expressing the 6F peptide (Tg6F) to a WD significantly reduced plasma total cholesterol and triglycerides (P < 0.0065). In a mouse model of colon cancer metastatic to the lungs, adding 0.06% of Tg6F, but not a control tomato concentrate (EV), to standard mouse chow reduced tumor-associated neutrophils by 94 ± 1.1% (P = 0.0052), and reduced tumor burden by two-thirds (P = 0.0371). Adding 0.06% of either EV or Tg6F by weight to standard mouse chow significantly reduced tumor burden in a mouse model of ovarian cancer; however, Tg6F was significantly more effective (35% reduction for EV vs. 53% reduction for Tg6F; P = 0.0069). Providing the same dose of tomato concentrate to humans would require only two tablespoons three times daily making this a practical approach for testing oral apoA-I mimetic therapy in the treatment of dyslipidemia and cancer.

Keywords: ApoA-I mimetic peptides; cancer; drug delivery; lipids; transgenic tomatoes

References

  1. J Biol Chem. 2007 Jul 6;282(27):19493-501 - PubMed
  2. J Immunol. 2008 Nov 15;181(10):7147-56 - PubMed
  3. J Exp Med. 1995 Jan 1;181(1):435-40 - PubMed
  4. Am J Obstet Gynecol. 2009 Jun;200(6):639.e1-5 - PubMed
  5. Nat Med. 2010 Feb;16(2):219-23 - PubMed
  6. J Sci Food Agric. 2014 Nov;94(14):2921-8 - PubMed
  7. Proc Natl Acad Sci U S A. 2003 Oct 14;100(21):12343-8 - PubMed
  8. Carcinogenesis. 2012 May;33(5):949-55 - PubMed
  9. J Lipid Res. 2013 Apr;54(4):995-1010 - PubMed
  10. Biochemistry. 2009 Dec 22;48(50):11858-71 - PubMed
  11. Prostaglandins Other Lipid Mediat. 2008 Dec;87(1-4):20-5 - PubMed
  12. Mol Cancer Ther. 2012 Jun;11(6):1311-9 - PubMed
  13. J Immunol. 2012 Mar 15;188(6):2749-58 - PubMed
  14. Proteomics. 2005 Nov;5(17):4589-96 - PubMed
  15. Nat Rev Immunol. 2014 Oct;14(10):667-85 - PubMed
  16. J Pharmacol Exp Ther. 2012 Aug;342(2):255-62 - PubMed
  17. J Lipid Res. 2015 Apr;56(4):871-87 - PubMed
  18. Am J Clin Nutr. 2005 Jan;81(1):122-9 - PubMed
  19. J Immunol. 2013 Apr 1;190(7):3798-805 - PubMed
  20. Am J Obstet Gynecol. 2008 Sep;199(3):215-23 - PubMed
  21. J Lipid Res. 2013 Dec;54(12 ):3403-18 - PubMed
  22. J Lipid Res. 2014 Oct;55(10):2053-63 - PubMed
  23. Ann Nutr Metab. 2003;47(2):64-9 - PubMed
  24. Integr Biol (Camb). 2011 Apr;3(4):479-89 - PubMed
  25. Crit Rev Food Sci Nutr. 1999 Sep;39(5):441-56 - PubMed
  26. J Biol Chem. 2013 Jul 19;288(29):21237-52 - PubMed
  27. Int J Cancer. 2010 Apr 15;126(8):1788-96 - PubMed
  28. J Agric Food Chem. 2009 Jun 24;57(12):5257-64 - PubMed
  29. Oncoimmunology. 2013 Jun 1;2(6):e24461 - PubMed
  30. Endocr Relat Cancer. 2007 Sep;14(3):755-67 - PubMed
  31. Proc Natl Acad Sci U S A. 2010 Nov 16;107(46):19997-20002 - PubMed
  32. Nature. 2008 Jul 24;454(7203):436-44 - PubMed
  33. Cell. 2010 Apr 2;141(1):39-51 - PubMed
  34. Gut. 2011 Aug;60(8):1094-102 - PubMed
  35. Int J Cancer. 2012 Mar 1;130(5):1071-81 - PubMed

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