RESUMEN
Inflammation and oxidative stress are related to cancer initiation and progression. We hypothesized that dietary supplementation with a procyanidin-rich Pinus pinaster extract (Pyc) with known antioxidant and anti-inflammatory effects could induce systemic protection, thereby attenuating tumor development. To test our hypothesis, mice were subjected to long-term supplementation (20 days, every 24 h) with saline, 25 mg/kg resveratrol or 100 mg/kg Pyc. Pyc was administered at a maximum tolerated oral dose, previously determined using toxicity indicators. Ten days after Ehrlich ascites tumor induction, weight gain and abdominal circumference increase were calculated. Ascitic fluid from six mice/group was evaluated by determining total volume; tumor packed cell volume; cell viability; tumor cell death type; inflammatory infiltrate; and levels of tumor necrosis factor alpha (TNF-α), interleukin 1 beta (IL-1ß), carbonyl proteins, lipid peroxidation, cyclooxigenase-2 (COX-2) expression and Akt phosphorylation (p-Akt). Ten mice/group were monitored to evaluate survival. Pyc and resveratrol were associated with reduced weight gain (>30%), abdominal circumference and ascitic volume. Tumor packed cell volume was reduced in Pyc-supplemented mice (26%), which had the largest tumor cell count reduction (>35%), increased ascitic fluid apoptosis rates (20%) and the longest survival (>2-fold). Pyc and resveratrol treatment both reduced inflammatory infiltrate and levels of TNF-α, IL-1ß, carbonyl proteins, lipid peroxidation (~ 30%) and p-Akt (up to 4-fold). Only Pyc significantly inhibited COX-2. Pyc attenuated oxidative and inflammation mediators and impaired tumor development, supporting our hypothesis and suggesting Pyc as a candidate for future studies in multitargeted dietary-based cancer prevention approaches.