title: Efficacy of tomato concentrates in mouse models of dyslipidemia and cancer.
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.
authors.affiliation: Division of Cardiology, Department of Medicine, David Geffen School of Medicine at UCLA Los Angeles, California, 90095-1736.
authors.forename: Arnab
authors.initials: A
authors.lastname: Chattopadhyay
authors.affiliation: Division of Cardiology, Department of Medicine, David Geffen School of Medicine at UCLA Los Angeles, California, 90095-1736.
authors.forename: Victor
authors.initials: V
authors.lastname: Grijalva
authors.affiliation: Division of Cardiology, Department of Medicine, David Geffen School of Medicine at UCLA Los Angeles, California, 90095-1736.
authors.forename: Greg
authors.initials: G
authors.lastname: Hough
authors.affiliation: Department of Obstetrics and Gynecology, David Geffen School of Medicine at UCLA Los Angeles, California, 90095-1736.
authors.forename: Feng
authors.initials: F
authors.lastname: Su
authors.affiliation: Division of Cardiology, Department of Medicine, David Geffen School of Medicine at UCLA Los Angeles, California, 90095-1736.
authors.forename: Pallavi
authors.initials: P
authors.lastname: Mukherjee
authors.affiliation: Department of Obstetrics and Gynecology, David Geffen School of Medicine at UCLA Los Angeles, California, 90095-1736.
authors.forename: Robin
authors.initials: R
authors.lastname: Farias-Eisner
authors.affiliation: Department of Medicine, University of Alabama at Birmingham Birmingham, Alabama, 35294.
authors.forename: G M
authors.initials: GM
authors.lastname: Anantharamaiah
authors.affiliation: Semel Institute for Neuroscience and Human Behavior, David Geffen School of Medicine at UCLA Los Angeles, California, 90095-1736.
authors.forename: Kym F
authors.initials: KF
authors.lastname: Faull
authors.affiliation: Semel Institute for Neuroscience and Human Behavior, David Geffen School of Medicine at UCLA Los Angeles, California, 90095-1736.
authors.forename: Lin H
authors.initials: LH
authors.lastname: Hwang
authors.affiliation: Division of Cardiology, Department of Medicine, David Geffen School of Medicine at UCLA Los Angeles, California, 90095-1736.
authors.forename: Mohamad
authors.initials: M
authors.lastname: Navab
authors.affiliation: Division of Cardiology, Department of Medicine, David Geffen School of Medicine at UCLA Los Angeles, California, 90095-1736.
authors.forename: Alan M
authors.initials: AM
authors.lastname: Fogelman
authors.affiliation: 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.
authors.forename: Srinivasa T
authors.initials: ST
authors.lastname: Reddy
keywords: ApoA-I mimetic peptides; cancer; drug delivery; lipids; transgenic tomatoes