Effect of low-fat diets on plasma levels of NF-κB-regulated inflammatory cytokines and angiogenic factors in men with prostate cancer

Abstract

Diet, nutritional status, and certain dietary supplements are postulated to influence the development and progression of prostate cancer. Angiogenesis and inflammation are central to tumor growth and progression, but the effect of diet on these processes remains uncertain. We explored changes in 50 plasma cytokines and angiogenic factors (CAF) in 145 men with prostate cancer enrolled in a preoperative, randomized controlled phase II trial with four arms: control (usual diet), low-fat (LF) diet, flaxseed-supplemented (FS) diet, and FS+LS diet. The mean duration of dietary intervention was 30 to 31 days. Among the individual arms, the largest number of significant changes (baseline vs. preoperative follow-up) was observed in the LF arm, with 19 CAFs decreasing and one increasing (P < 0.05). Compared with the control arm, 6 CAFs-including proangiogenic factors (stromal-cell derived-1α) and myeloid factors (granulocyte-colony-stimulating factor, macrophage colony-stimulating factor)-all decreased in the LF arm compared with controls; three and four CAFs changed in the FS and FS+LF arms, respectively. Weight loss occurred in the LF arms and significantly correlated with VEGF decreases (P < 0.001). The CAFs that changed in the LF arm are all known to be regulated by NF-κB, and a pathway analysis identified NF-κB as the most likely regulatory network associated with these changes in the LF arm but not in the FS-containing arms. These results suggest that a LF diet without flaxseed may reduce levels of specific inflammatory CAFs and suggests that the NF-κB pathway may be a mediator of these changes.

Conflict of interest statement

Disclosure of Potential Conflicts of Interest

Figures

Fig. 1

Clinical Trial Design Scheme of randomized, controlled trial of low-fat and/or flaxseed supplemented diets in men with prostate cancer (30). Prostate cancer patients were randomly assigned to control (C), flaxseed-supplemented diet (FS), low-fat diet (LF), or flaxseed-supplemented, low-fat diet (FS+LF). The blue arrows indicate the collection of plasma samples, collected at the prestudy evaluation and at follow-up (within 3 days of surgery) and prostate tissue (collected at least 14 days before baseline and during the prostatectomy).

Fig. 2

Distinctive CAF changes following low-fat and flaxseed supplemented diet. The percent change in mean differences between the control arm and the treatment arm are shown. CAF mean differences were derived for each participant by subtracting the baseline from the follow-up for that biomarker.

Fig. 3

Unsupervised clustering identified coordinate changes in 6 CAFs in the LF arm. A. Relative mean differences of 6 CAFs are shown (red indicates high levels, green indicates low levels). CAF levels from patients in the control arm are grouped to the left under the blue bar and patients in the LF arm are under the red bar. B. Functional interacting network among the identified CAFs that changed in the LF arm compared to control. Pathway analysis was performed on 6 CAFs that significantly changed in the LF arm compared to the control arm (P

Fig. 4

Correlation between CAFs and body mass index. Correlation scatterplot of changes in concentrations of VEGF correlating with changes in body mass index (BMI). The correlation was tested by Pearson’s correlation.

Fig. 5

Changes in expression of tumor correlative markers in prostate cancer after diet modulation. The ability of LF diet, FS diet or the combination diet to affect changes in the prostate was determined by immunohistochemical staining for (A) VEGF, (B) CA-9, (C) NF-κB and (D) COX-2. Data are graphed as percent positive cells, *p