Dietary supplementation with procyanidin-rich Pinus pinaster extract is associated with attenuated Ehrlich tumor development in mice.
Avainsanat
Abstrakti
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-1β), 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-1β, 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.