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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

Both the control tomato concentrate (EV) and the tomato concentrate containing the 6F peptide (Tg6F) significantly reduced ovarian cancer cell tumor burden, but the tomato concentrate containing the 6F peptide was significantly more effective. Female C57BL/6J mice at age 9 weeks (n = 24 per group) were given an intraperitoneal injection containing 8 × 106 ID8 cells in a total volume of 0.8 mL of DMEM (without supplements). Following injection of the ID8 cells 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 containing 0.06% by weight of the transgenic 6F tomato concentrate (Tg6F), which provided the mice with a dose of the 6F peptide of ∼7 mg/kg per day. After 12 weeks the mice were subjected to a terminal bleed, and after sacrifice the number of tumor nodules on peritoneal surfaces and on the surface of abdominal organs was determined as described in Materials and Methods. (A) The total number of tumor nodules in the abdomen. (B) The number of tumor nodules on the surface of the peritoneal cavity. (C) Number of tumor nodules on the diaphragm. (D) The number of tumor nodules on the surface of the intestine. (E) The number of tumor nodules in the abdomen that were greater than 1 mm in size. The data shown are mean ± SEM; NS, not significant. These results are representative of two of two experiments.
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fig05: Both the control tomato concentrate (EV) and the tomato concentrate containing the 6F peptide (Tg6F) significantly reduced ovarian cancer cell tumor burden, but the tomato concentrate containing the 6F peptide was significantly more effective. Female C57BL/6J mice at age 9 weeks (n = 24 per group) were given an intraperitoneal injection containing 8 × 106 ID8 cells in a total volume of 0.8 mL of DMEM (without supplements). Following injection of the ID8 cells 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 containing 0.06% by weight of the transgenic 6F tomato concentrate (Tg6F), which provided the mice with a dose of the 6F peptide of ∼7 mg/kg per day. After 12 weeks the mice were subjected to a terminal bleed, and after sacrifice the number of tumor nodules on peritoneal surfaces and on the surface of abdominal organs was determined as described in Materials and Methods. (A) The total number of tumor nodules in the abdomen. (B) The number of tumor nodules on the surface of the peritoneal cavity. (C) Number of tumor nodules on the diaphragm. (D) The number of tumor nodules on the surface of the intestine. (E) The number of tumor nodules in the abdomen that were greater than 1 mm in size. The data shown are mean ± SEM; NS, not significant. These results are representative of two of two experiments.

Mentions: In a mouse model of ovarian cancer in which mouse ovarian cancer cells were injected into the peritoneum of female mice with normal immune function, the total number of tumor nodules in the abdomen was significantly reduced by approximately 35% in mice receiving EV (P = 0.0013) compared to mice receiving standard mouse chow alone (Fig.5A). In the mice receiving Tg6F, the total number of tumor nodules in the abdomen was reduced by approximately 53% (P < 0.0001) compared to mice receiving standard mouse chow alone (Fig.5A). The difference between the total number of tumor nodules in the abdomen of mice receiving EV compared to those receiving Tg6F was highly significant (P = 0.0069) (Fig.5A).


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)

Both the control tomato concentrate (EV) and the tomato concentrate containing the 6F peptide (Tg6F) significantly reduced ovarian cancer cell tumor burden, but the tomato concentrate containing the 6F peptide was significantly more effective. Female C57BL/6J mice at age 9 weeks (n = 24 per group) were given an intraperitoneal injection containing 8 × 106 ID8 cells in a total volume of 0.8 mL of DMEM (without supplements). Following injection of the ID8 cells 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 containing 0.06% by weight of the transgenic 6F tomato concentrate (Tg6F), which provided the mice with a dose of the 6F peptide of ∼7 mg/kg per day. After 12 weeks the mice were subjected to a terminal bleed, and after sacrifice the number of tumor nodules on peritoneal surfaces and on the surface of abdominal organs was determined as described in Materials and Methods. (A) The total number of tumor nodules in the abdomen. (B) The number of tumor nodules on the surface of the peritoneal cavity. (C) Number of tumor nodules on the diaphragm. (D) The number of tumor nodules on the surface of the intestine. (E) The number of tumor nodules in the abdomen that were greater than 1 mm in size. 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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fig05: Both the control tomato concentrate (EV) and the tomato concentrate containing the 6F peptide (Tg6F) significantly reduced ovarian cancer cell tumor burden, but the tomato concentrate containing the 6F peptide was significantly more effective. Female C57BL/6J mice at age 9 weeks (n = 24 per group) were given an intraperitoneal injection containing 8 × 106 ID8 cells in a total volume of 0.8 mL of DMEM (without supplements). Following injection of the ID8 cells 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 containing 0.06% by weight of the transgenic 6F tomato concentrate (Tg6F), which provided the mice with a dose of the 6F peptide of ∼7 mg/kg per day. After 12 weeks the mice were subjected to a terminal bleed, and after sacrifice the number of tumor nodules on peritoneal surfaces and on the surface of abdominal organs was determined as described in Materials and Methods. (A) The total number of tumor nodules in the abdomen. (B) The number of tumor nodules on the surface of the peritoneal cavity. (C) Number of tumor nodules on the diaphragm. (D) The number of tumor nodules on the surface of the intestine. (E) The number of tumor nodules in the abdomen that were greater than 1 mm in size. The data shown are mean ± SEM; NS, not significant. These results are representative of two of two experiments.
Mentions: In a mouse model of ovarian cancer in which mouse ovarian cancer cells were injected into the peritoneum of female mice with normal immune function, the total number of tumor nodules in the abdomen was significantly reduced by approximately 35% in mice receiving EV (P = 0.0013) compared to mice receiving standard mouse chow alone (Fig.5A). In the mice receiving Tg6F, the total number of tumor nodules in the abdomen was reduced by approximately 53% (P < 0.0001) compared to mice receiving standard mouse chow alone (Fig.5A). The difference between the total number of tumor nodules in the abdomen of mice receiving EV compared to those receiving Tg6F was highly significant (P = 0.0069) (Fig.5A).

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