First human study of oral anthocyanins, antiangiogenic compounds found in certain foods, shows activity for colorectal cancer chemoprevention
September 14, 2010 Leave a comment
Anthocyanins are naturally occurring pigmented chemicals belonging to the group of molecules called polyphenols found in green tea, many kinds of berries and fruits, and spices, such as curcumin.
These compounds have been shown to possess chemopreventive activity against a variety of cancerous tumors in preclinical studies, including tumors of the gastrointestinal tract. The cancer preventive properties are believed to be attributable to both their antiangiogenic effect, preventing tumors from developing a blood supply, as well as direct anti-tumor activity.
Researchers at the University of Leicester in the UK have conducted a first-in-human pilot study of mirtocyan, an anthocyanin-rich standardized extract from bilberries, in a small group of patients with colorectal cancer (CRC) to determine whether its administration can also impact existing large tumors.
The study also examined whether oral intake of mirtocyan generates measurable levels of bilberry anthocyanins in the blood, urine, and tumor tissue. Fifteen patients with colorectal adenocarcinomas and 10 with CRC liver metastases were enrolled in this British study1.The patients that were scheduled to undergo surgical removal of a primary colon tumor or liver metastases were given oral mirtocyan at 3 different doses — 1.4, 2.8, or 5.6 grams (containing 0.5-2.0 grams anthocyanins) — on a daily basis for 7 days before surgery. The amount of bilberry anthocyanins present in body tissue and fluids after oral intake was analyzed by high performance liquid chromatography (HPLC) with visible or mass spectrometric detection. The researchers measured the rate by which the cancer cells divide by immunohistochemistry (Ki67) in tumor samples taken during surgery.
They also measured concentrations of insulin-like growth factor (IGF-I) in the patients’ plasma — IGF-1 stimulates angiogenesis through its upregulation of VEGF (vascular endothelial growth factor), a potent angiogenesis factor that stimulates the tumor blood supply. Tumor proliferation from colorectal tumor samples taken from all patients who received mirtocyan was significantly decreased by 7% compared with pre-intervention values. There was also a small reduction in circulating IGF-I concentrations across all patients/doses and a small increase in apoptosis in colorectal tumor samples. Mirtocyan anthocyanins and its metabolites were identified in plasma, colorectal tissue, and urine of patients, but not in the liver.
Anthocyanin concentrations in the plasma and urine were roughly dose-dependent, based on the amount taken by mouth, reaching approximately 179 ng/gram in tumor tissue at the highest dose of mirtocyan. While this was a small study, involving only 25 cancer patients, and lacked a control group, it demonstrates the feasibility of measuring the anti-tumor effects of antiangiogenic molecules from food sources in cancer patients2. It is possible that higher concentrations of anthocyanin would lead to even more pronounced anti-tumor effects.
The levels of anthocyanin metabolites detected in the tumor samples in this study were much lower than those previously published in mice experiments, suggesting that testing higher doses of mirtocyan should be done to identify a dose-dependent effect.
However, the evidence this study generates, showing biological activity against colorectal tumors in cancer patients suggests that foods and their extracts containing anthocyanins, and mirtocyan, specifically, have potential to improve cancer treatment through non-pharmaceutical means. Larger randomized, controlled studies would be required to establish this benefit.
By Roderick Smith, M.S.
1. Thomasset S, Berry DP, Cai H, et al. Pilot study of oral anthocyanins for colorectal cancer chemoprevention. Cancer Prev Res 2009;2(7):625-33.
2. Meyskens Jr. FL. Food extracts for chemoprevention: Quo Vadis? Cancer Prev Res 2009;2(7):608-10.