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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

Plasma lipids and plasma serum amyloid A (SAA) levels in mice after intraperitoneal injection of ovarian cancer cells. Plasma lipid levels and SAA levels were measured in the mice described in Figure5. (A) Plasma total cholesterol levels. (B) The linear correlation between plasma total cholesterol levels and the total number of tumors in the abdomen. (C) Plasma triglyceride levels. (D) The linear correlation between plasma triglyceride levels and the total number of tumors in the abdomen. (E) Plasma HDL-cholesterol levels. (F) The linear correlation between plasma HDL-cholesterol levels and the total number of tumors in the abdomen. (G) Plasma apoA-I levels. (H) The linear correlation between plasma apoA-I levels and the total number of tumors in the abdomen. (I) plasma serum amyloid A (SAA) levels. (J) The linear correlation between plasma SAA levels and the total number of tumors in the abdomen. The data shown in the bar graphs are mean ± SEM; NS, not significant. This experiment was done once.
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fig06: Plasma lipids and plasma serum amyloid A (SAA) levels in mice after intraperitoneal injection of ovarian cancer cells. Plasma lipid levels and SAA levels were measured in the mice described in Figure5. (A) Plasma total cholesterol levels. (B) The linear correlation between plasma total cholesterol levels and the total number of tumors in the abdomen. (C) Plasma triglyceride levels. (D) The linear correlation between plasma triglyceride levels and the total number of tumors in the abdomen. (E) Plasma HDL-cholesterol levels. (F) The linear correlation between plasma HDL-cholesterol levels and the total number of tumors in the abdomen. (G) Plasma apoA-I levels. (H) The linear correlation between plasma apoA-I levels and the total number of tumors in the abdomen. (I) plasma serum amyloid A (SAA) levels. (J) The linear correlation between plasma SAA levels and the total number of tumors in the abdomen. The data shown in the bar graphs are mean ± SEM; NS, not significant. This experiment was done once.

Mentions: In contrast to the case in the metastatic colon cancer model (Fig.3C), and in contrast to our previous studies with the 4F peptide (Su et al. 2010, 2012) there was no significant change in the levels of plasma LPA species (data not shown). Similarly, there was no significant difference in total plasma cholesterol levels in mice receiving EV compared to Tg6F (Fig.6A), and plasma total cholesterol levels did not correlate with the total number of tumor nodules (Fig.6B). However, plasma triglyceride levels were significantly reduced in mice receiving either tomato concentrate compared to mice receiving standard mouse chow alone, and there was no significant difference in plasma triglyceride levels in mice receiving EV compared to Tg6F (Fig.6C). The total number of tumor nodules was significantly and positively correlated with plasma triglyceride levels (r2 = 0.1375; P = 0.0022) (Fig.6D). Plasma HDL-cholesterol levels were significantly higher in mice receiving either tomato concentrate compared to mice receiving standard mouse chow alone, and there was no significant difference in the HDL-cholesterol levels in mice receiving EV compared to Tg6F (Fig.6E). HDL-cholesterol levels were not significantly correlated with the total number of tumor nodules (Fig.6F). Plasma apoA-I levels were significantly higher in mice receiving either tomato concentrate compared to mice receiving chow alone, and there was no significant difference in the apoA-I levels in mice receiving EV compared to Tg6F (Fig.6G). Consistent with our previous data (Su et al. 2010) and that of Zamanian-Daryoush et al. (2013), plasma apoA-I levels were inversely and significantly correlated with the total number of tumor nodules (r2 = 0.1096; P = 0.0062) (Fig.6H). Plasma SAA levels were significantly lower in mice receiving either tomato concentrate compared to mice receiving chow alone, and there was no significant difference in SAA levels in mice receiving EV compared to Tg6F (Fig.6I). Plasma SAA levels were weakly but significantly correlated with the total number of tumor nodules (r2 = 0.06950; P = 0.0325) (Fig.6J).


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)

Plasma lipids and plasma serum amyloid A (SAA) levels in mice after intraperitoneal injection of ovarian cancer cells. Plasma lipid levels and SAA levels were measured in the mice described in Figure5. (A) Plasma total cholesterol levels. (B) The linear correlation between plasma total cholesterol levels and the total number of tumors in the abdomen. (C) Plasma triglyceride levels. (D) The linear correlation between plasma triglyceride levels and the total number of tumors in the abdomen. (E) Plasma HDL-cholesterol levels. (F) The linear correlation between plasma HDL-cholesterol levels and the total number of tumors in the abdomen. (G) Plasma apoA-I levels. (H) The linear correlation between plasma apoA-I levels and the total number of tumors in the abdomen. (I) plasma serum amyloid A (SAA) levels. (J) The linear correlation between plasma SAA levels and the total number of tumors in the abdomen. The data shown in the bar graphs are mean ± SEM; NS, not significant. This experiment was done once.
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Related In: Results  -  Collection

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fig06: Plasma lipids and plasma serum amyloid A (SAA) levels in mice after intraperitoneal injection of ovarian cancer cells. Plasma lipid levels and SAA levels were measured in the mice described in Figure5. (A) Plasma total cholesterol levels. (B) The linear correlation between plasma total cholesterol levels and the total number of tumors in the abdomen. (C) Plasma triglyceride levels. (D) The linear correlation between plasma triglyceride levels and the total number of tumors in the abdomen. (E) Plasma HDL-cholesterol levels. (F) The linear correlation between plasma HDL-cholesterol levels and the total number of tumors in the abdomen. (G) Plasma apoA-I levels. (H) The linear correlation between plasma apoA-I levels and the total number of tumors in the abdomen. (I) plasma serum amyloid A (SAA) levels. (J) The linear correlation between plasma SAA levels and the total number of tumors in the abdomen. The data shown in the bar graphs are mean ± SEM; NS, not significant. This experiment was done once.
Mentions: In contrast to the case in the metastatic colon cancer model (Fig.3C), and in contrast to our previous studies with the 4F peptide (Su et al. 2010, 2012) there was no significant change in the levels of plasma LPA species (data not shown). Similarly, there was no significant difference in total plasma cholesterol levels in mice receiving EV compared to Tg6F (Fig.6A), and plasma total cholesterol levels did not correlate with the total number of tumor nodules (Fig.6B). However, plasma triglyceride levels were significantly reduced in mice receiving either tomato concentrate compared to mice receiving standard mouse chow alone, and there was no significant difference in plasma triglyceride levels in mice receiving EV compared to Tg6F (Fig.6C). The total number of tumor nodules was significantly and positively correlated with plasma triglyceride levels (r2 = 0.1375; P = 0.0022) (Fig.6D). Plasma HDL-cholesterol levels were significantly higher in mice receiving either tomato concentrate compared to mice receiving standard mouse chow alone, and there was no significant difference in the HDL-cholesterol levels in mice receiving EV compared to Tg6F (Fig.6E). HDL-cholesterol levels were not significantly correlated with the total number of tumor nodules (Fig.6F). Plasma apoA-I levels were significantly higher in mice receiving either tomato concentrate compared to mice receiving chow alone, and there was no significant difference in the apoA-I levels in mice receiving EV compared to Tg6F (Fig.6G). Consistent with our previous data (Su et al. 2010) and that of Zamanian-Daryoush et al. (2013), plasma apoA-I levels were inversely and significantly correlated with the total number of tumor nodules (r2 = 0.1096; P = 0.0062) (Fig.6H). Plasma SAA levels were significantly lower in mice receiving either tomato concentrate compared to mice receiving chow alone, and there was no significant difference in SAA levels in mice receiving EV compared to Tg6F (Fig.6I). Plasma SAA levels were weakly but significantly correlated with the total number of tumor nodules (r2 = 0.06950; P = 0.0325) (Fig.6J).

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