Anticarcinogenic properties of garlic and its sulfur components in the rat and in human cells.
Institut National de la Recherche Agronomique, UMR de Toxicologie Alimentaire, Dijon, France
AIM: Garlic has long been demonstrated to have prophylactic and therapeutic properties. The possibility that garlic may have an impact on the incidence of human cancer is gaining support from both experimental studies and epidemiological findings. As a part of the European project " Garlic and Health " (QLK1-CT-1999-498), a set of studies was performed in the rat in order to further investigate the roles of garlic on different biological events involved in chemical carcinogenesis: the bio-activation or detoxification of carcinogens, the alteration of DNA and the development of preneoplasic foci. In a second step, preventive properties of garlic sulfur compounds were studied in human, using the human derived hepatoma (HepG2) cell line. METHODS: In vivo studies were carried out in Wistar rats fed with different garlic powders for two weeks (5% of the diet). The activity and the levels of several phase I enzymes (cytochromes P450 (CYP)) and phase II enzymes (transferases, quinone reductase) were measured in the liver. The antigenotoxic effects of garlic were evaluated in the liver and the colon of rats after treatment by different genotoxic compounds (nitrosamines, aflatoxin B1). The comet assay was used to quantify DNA damage. The capacities of garlic powders to reduce the initiation stage of carcinogenesis was assessed using a two-step medium term hepatocarcinogenesis protocol. In the in vitro study, HepG2 cells were first treated with the sulfur compound then were treated with the genotoxic compound. DNA damage was assessed using the comet assay. RESULTS: Garlic powder administration to rats modified hepatic enzymes involved in carcinogen metabolism : an increase of CYP 1A2 and phase II enzymes activities such as glutathion S-transferase and UDP glucuronosyltransferase and a reduction of CYP 2E1 activity were observed. A significant reduction of genotoxicity of chemicals which are metabolized by these enzymes (nitrosamines, aflatoxin B1) was observed in the liver and the colon of rats fed garlic powders. In addition, consumption of garlic decreased the appearance of hepatic preneoplasic foci induced by administration of aflatoxin B1. The anticarcinogenic efficacy is correlated with the sulfur content of garlic. In the human cell line HepG2, garlic sulfur compounds were shown to prevent the genotoxicity of aflatoxin B1 and dimethylnitrosamine. CONCLUSIONS: Taken together, these results show that the anticarcinogenic action of garlic is partly due to a reduction of the genotoxicity of carcinogens which is a consequence of the modulation of enzymes involved in activation/detoxication of the genotoxic compounds. These effects have been observed in vivo, in the rat, and in vitro, in a human cell line. This corroborates the assumption that garlic could play an important role in cancer prevention by the diet. A human intervention study is in progress to confirm this hypothesis.
Paper presented at the International Symposium on Predictive Oncology and Intervention Strategies; Nice, France; February 7 - 10, 2004; in poster session 997 (Chemoprevention).