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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

Tomato concentrate containing the 6F peptide (Tg6F), but not control tomato concentrate (EV) reduced metastasis of colon cancer cells to the lungs. Female BALB/c mice 6 weeks of age (n = 12 per group) were injected with 2 × 104 CT26 cells in 100 μL of PBS via tail vein as described in Materials and Methods. After injection, the mice were maintained on either standard mouse chow (Chow), or standard mouse chow containing 0.06% by weight of the control transgenic tomato concentrate (EV), or standard mouse chow containing 0.06% by weight of the transgenic 6F tomato concentrate (Tg6F), which provided the mice with a dose of tomato concentrate of ∼120 mg/kg per day per mouse, which provided the mice with a dose of the 6F peptide of ∼7 mg/kg per day. After 4 weeks the mice were subjected to a terminal bleed, and after sacrifice the lungs were harvested, weighed, and fixed with Bouin’s solution, and the number of tumor nodules on the surface of the lungs was determined as described in Materials and Methods. (A) Weight of the lungs in grams. (B) Number of tumor nodules on the surface of the lungs. (C) Plasma levels of lysophosphatidic acid 20:4 (LPA 20:4). The data shown are mean ± SEM; NS, not significant. These results are representative of two of two experiments.
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fig03: Tomato concentrate containing the 6F peptide (Tg6F), but not control tomato concentrate (EV) reduced metastasis of colon cancer cells to the lungs. Female BALB/c mice 6 weeks of age (n = 12 per group) were injected with 2 × 104 CT26 cells in 100 μL of PBS via tail vein as described in Materials and Methods. After injection, the mice were maintained on either standard mouse chow (Chow), or standard mouse chow containing 0.06% by weight of the control transgenic tomato concentrate (EV), or standard mouse chow containing 0.06% by weight of the transgenic 6F tomato concentrate (Tg6F), which provided the mice with a dose of tomato concentrate of ∼120 mg/kg per day per mouse, which provided the mice with a dose of the 6F peptide of ∼7 mg/kg per day. After 4 weeks the mice were subjected to a terminal bleed, and after sacrifice the lungs were harvested, weighed, and fixed with Bouin’s solution, and the number of tumor nodules on the surface of the lungs was determined as described in Materials and Methods. (A) Weight of the lungs in grams. (B) Number of tumor nodules on the surface of the lungs. (C) Plasma levels of lysophosphatidic acid 20:4 (LPA 20:4). The data shown are mean ± SEM; NS, not significant. These results are representative of two of two experiments.

Mentions: The weight of the lungs after intravenous administration of the colon cancer cells was significantly less after administration of Tg6F compared to mice not receiving any tomato concentrate, or compared to mice receiving EV (Fig.3A). The number of tumor nodules on the surface of the lungs was less after administration of EV, but this did not reach statistical significance (Fig.3B). In contrast, there was a significant and remarkable two-thirds reduction in the number of tumor nodules on the surface of the lungs after administration of Tg6F (Fig.3B). Consistent with our previous report on the efficacy of the 4F peptide in this model (Su et al. 2012), the plasma levels of LPA 20:4 were significantly reduced with administration of Tg6F, but plasma LPA 20:4 levels were not decreased with administration of EV (Fig.3C). The plasma levels of other LPA species including LPA 18:2, LPA 18:1, and LPA 18:0 were not significantly reduced (data not shown).


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)

Tomato concentrate containing the 6F peptide (Tg6F), but not control tomato concentrate (EV) reduced metastasis of colon cancer cells to the lungs. Female BALB/c mice 6 weeks of age (n = 12 per group) were injected with 2 × 104 CT26 cells in 100 μL of PBS via tail vein as described in Materials and Methods. After injection, the mice were maintained on either standard mouse chow (Chow), or standard mouse chow containing 0.06% by weight of the control transgenic tomato concentrate (EV), or standard mouse chow containing 0.06% by weight of the transgenic 6F tomato concentrate (Tg6F), which provided the mice with a dose of tomato concentrate of ∼120 mg/kg per day per mouse, which provided the mice with a dose of the 6F peptide of ∼7 mg/kg per day. After 4 weeks the mice were subjected to a terminal bleed, and after sacrifice the lungs were harvested, weighed, and fixed with Bouin’s solution, and the number of tumor nodules on the surface of the lungs was determined as described in Materials and Methods. (A) Weight of the lungs in grams. (B) Number of tumor nodules on the surface of the lungs. (C) Plasma levels of lysophosphatidic acid 20:4 (LPA 20:4). The data shown are mean ± SEM; NS, not significant. These results are representative of two of two experiments.
© Copyright Policy - open-access
Related In: Results  -  Collection

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fig03: Tomato concentrate containing the 6F peptide (Tg6F), but not control tomato concentrate (EV) reduced metastasis of colon cancer cells to the lungs. Female BALB/c mice 6 weeks of age (n = 12 per group) were injected with 2 × 104 CT26 cells in 100 μL of PBS via tail vein as described in Materials and Methods. After injection, the mice were maintained on either standard mouse chow (Chow), or standard mouse chow containing 0.06% by weight of the control transgenic tomato concentrate (EV), or standard mouse chow containing 0.06% by weight of the transgenic 6F tomato concentrate (Tg6F), which provided the mice with a dose of tomato concentrate of ∼120 mg/kg per day per mouse, which provided the mice with a dose of the 6F peptide of ∼7 mg/kg per day. After 4 weeks the mice were subjected to a terminal bleed, and after sacrifice the lungs were harvested, weighed, and fixed with Bouin’s solution, and the number of tumor nodules on the surface of the lungs was determined as described in Materials and Methods. (A) Weight of the lungs in grams. (B) Number of tumor nodules on the surface of the lungs. (C) Plasma levels of lysophosphatidic acid 20:4 (LPA 20:4). The data shown are mean ± SEM; NS, not significant. These results are representative of two of two experiments.
Mentions: The weight of the lungs after intravenous administration of the colon cancer cells was significantly less after administration of Tg6F compared to mice not receiving any tomato concentrate, or compared to mice receiving EV (Fig.3A). The number of tumor nodules on the surface of the lungs was less after administration of EV, but this did not reach statistical significance (Fig.3B). In contrast, there was a significant and remarkable two-thirds reduction in the number of tumor nodules on the surface of the lungs after administration of Tg6F (Fig.3B). Consistent with our previous report on the efficacy of the 4F peptide in this model (Su et al. 2012), the plasma levels of LPA 20:4 were significantly reduced with administration of Tg6F, but plasma LPA 20:4 levels were not decreased with administration of EV (Fig.3C). The plasma levels of other LPA species including LPA 18:2, LPA 18:1, and LPA 18:0 were not significantly reduced (data not shown).

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