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

Chattopadhyay A, Grijalva V, Hough G, Su F, Mukherjee P, Farias-Eisner R, Anantharamaiah GM, Faull KF, Hwang LH, Navab M, Fogelman AM, Reddy ST - Pharmacol Res Perspect (2015)

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: Division of Cardiology, Department of Medicine, David Geffen School of Medicine at UCLA Los Angeles, California, 90095-1736.

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.

No MeSH data available.


Related in: MedlinePlus

Tumor-associated neutrophils are dramatically reduced by tomato concentrate containing the 6F peptide (Tg6F), but not control tomato concentrate (EV) in a mouse model of colon cancer cells metastasizing to the lungs. Tumor-associated neutrophils in the lungs of the mice described in Figure3 were determined as described in Materials and Methods. (A) Representative examples from each treatment group. (B) The % area stained for Ly6G (mean ± SEM). NS, not significant. The experiment was done once.
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fig04: Tumor-associated neutrophils are dramatically reduced by tomato concentrate containing the 6F peptide (Tg6F), but not control tomato concentrate (EV) in a mouse model of colon cancer cells metastasizing to the lungs. Tumor-associated neutrophils in the lungs of the mice described in Figure3 were determined as described in Materials and Methods. (A) Representative examples from each treatment group. (B) The % area stained for Ly6G (mean ± SEM). NS, not significant. The experiment was done once.

Mentions: As early as 1995 evidence was accumulating that granulocytes could promote tumor growth (Pekarek et al. 1995). Tumor growth in the lungs was later shown to be promoted by neutrophil elastase (Houghton et al. 2010). Therefore, we determined the content of tumor-associated neutrophils in this mouse model of colon cancer cells metastasizing to the lungs. A representative photomicrograph of the tumor-associated neutrophils in each of the treatment groups is shown in Figure4A and the data are shown in Figure4B. Remarkably, addition of 0.06% by weight of Tg6F to the standard mouse chow reduced tumor associated neutrophils by 94 ± 1.1% (P = 0.0052).


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

Chattopadhyay A, Grijalva V, Hough G, Su F, Mukherjee P, Farias-Eisner R, Anantharamaiah GM, Faull KF, Hwang LH, Navab M, Fogelman AM, Reddy ST - Pharmacol Res Perspect (2015)

Tumor-associated neutrophils are dramatically reduced by tomato concentrate containing the 6F peptide (Tg6F), but not control tomato concentrate (EV) in a mouse model of colon cancer cells metastasizing to the lungs. Tumor-associated neutrophils in the lungs of the mice described in Figure3 were determined as described in Materials and Methods. (A) Representative examples from each treatment group. (B) The % area stained for Ly6G (mean ± SEM). NS, not significant. The experiment was done once.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4492730&req=5

fig04: Tumor-associated neutrophils are dramatically reduced by tomato concentrate containing the 6F peptide (Tg6F), but not control tomato concentrate (EV) in a mouse model of colon cancer cells metastasizing to the lungs. Tumor-associated neutrophils in the lungs of the mice described in Figure3 were determined as described in Materials and Methods. (A) Representative examples from each treatment group. (B) The % area stained for Ly6G (mean ± SEM). NS, not significant. The experiment was done once.
Mentions: As early as 1995 evidence was accumulating that granulocytes could promote tumor growth (Pekarek et al. 1995). Tumor growth in the lungs was later shown to be promoted by neutrophil elastase (Houghton et al. 2010). Therefore, we determined the content of tumor-associated neutrophils in this mouse model of colon cancer cells metastasizing to the lungs. A representative photomicrograph of the tumor-associated neutrophils in each of the treatment groups is shown in Figure4A and the data are shown in Figure4B. Remarkably, addition of 0.06% by weight of Tg6F to the standard mouse chow reduced tumor associated neutrophils by 94 ± 1.1% (P = 0.0052).

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: Division of Cardiology, Department of Medicine, David Geffen School of Medicine at UCLA Los Angeles, California, 90095-1736.

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.

No MeSH data available.


Related in: MedlinePlus