Grape seed extract dose-responsively decreases disease severity in a rat model of mucositis; concomitantly enhancing chemotherapeutic effectiveness in colon cancer cells

• Published in: PloS one Vol. 9; no. 1; p. e85184
• Main Authors: Cheah, Ker Yeaw, Howarth, Gordon Stanley, Bastian, Susan Elaine Putnam
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 21.01.2014; Public Library of Science (PLoS)
• Subjects: 5-Fluorouracil; Administration, Oral; Animal tissues; Animals; Antioxidants - pharmacology; Apoptosis; Biology; Biphenyl (Compound); Bromine compounds; Caco-2 Cells; Cancer; Cancer cells; Cancer therapies; Cell Proliferation - drug effects; Cell Survival - drug effects; Chemistry; Chemotherapy; Colon; Colon cancer; Colorectal cancer; Cytotoxicity; Female; Fluorouracil; Food; Gastroenterology; Gastrointestinal system; Gastrointestinal tract; Gene expression; Grape Seed Extract - pharmacology; Health aspects; Health services; Humans; Inflammation; Injections, Intraperitoneal; Intestinal Mucosa - drug effects; Intestinal Mucosa - enzymology; Intestinal Mucosa - pathology; Intestine; Jejunum; Jejunum - drug effects; Jejunum - enzymology; Jejunum - pathology; Kinases; Medicine; Metabolism; Mucosa; Mucositis; Mucositis - chemically induced; Mucositis - drug therapy; Mucositis - enzymology; Mucositis - pathology; Nutrition research; Peroxidase; Peroxidase - antagonists & inhibitors; Peroxidase - metabolism; Plant extracts; Polymerization; Rats; Rodents; Seeds; Severity of Illness Index; Signal transduction; Studies; Womens health; Australia; South Australia Australia
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0085184

Mucositis is a serious disorder of the gastrointestinal tract that results from cancer chemotherapy. We investigated the effects of increasing grape seed extract doses on the severity of chemotherapy in a rat model and its coincident impact on chemotherapeutic effectiveness in colon cancer cells. Female Dark Agouti rats were gavaged with grape seed extract (400-1000 mg/kg) or water (day 3-11) and were injected intraperitoneally with 5-Fluorouracil (150 mg/kg) or saline (control) on day 9 to induce mucositis. Daily metabolic data were collected and rats were sacrificed on day 12. Intestinal tissues were collected for histological and myeloperoxidase analyses. Caco-2 cell viability was examined in response to grape seed extract in combination with 5-Fluorouracil by 3-(4,5-Dimethylthiazol-2yl)-2,5-diphenyl-tetrazolium bromide) assay. Compared with 5-Fluorouracil controls, grape seed extract (400-1000 mg/kg) significantly decreased the histological damage score (P<0.05) in the jejunum. Grape seed extract (1000 mg/kg) increased jejunal crypt depth by 25% (P<0.05) in 5-Fluorouracil treated rats compared to 5-Fluorouracil controls, and attenuated the 5-Fluorouracil -induced reduction of mucosal thickness (25%, P<0.05). Grape seed extract (600 mg/kg) decreased myeloperoxidase activity by 55% (P<0.01) compared to 5-Fluorouracil controls. Grape seed extract was more effective at ameliorating 5-Fluorouracil induced intestinal injury, with effects most pronounced in the proximal jejunum. Grape seed extract (10-25 ug/mL) significantly enhanced the growth-inhibitory effects of 5-Fluorouracil by 26% (P<0.05) in Caco-2 cells and was more potent than 5-Fluorouracil at 50-100 µg/mL. Grape seed extract may represent a new therapeutic option to decrease the symptoms of intestinal mucositis while concurrently impacting on the viability of colon cancer cells.