TY - JOUR AB - Shoots of white asparagus are a popular vegetable dish, known to be rich in many bioactive phytochemicals reported to possess antioxidant, and anti-inflammatory and antitumor activities. We evaluated the anticancer mechanisms of a methanolic extract of Asparagus officinalis L. shoots (Asp) on human colon carcinoma cells (SW480) and their derived metastatic cells (SW620), and Asp chemopreventive properties were also assessed in a model of colon carcinogenesis. SW480 and SW620 cell proliferation was inhibited by 80% after exposure to Asp (80 µg/ml). We demonstrated that Asp induced cell death through the activation of TRAIL DR4/DR5 death receptors leading to the activation of caspase-8 and caspase-3 and to cell apoptosis. By specific blocking agents of DR4/DR5 receptors we were able to prevent Asp-triggered cell death confirming the key role of DR4/DR5 receptors. We found also that Asp (80 µg/ml) was able to potentiate the effects of the cytokine TRAIL on cell death even in the TRAIL-resistant metastatic SW620 cells. Colon carcinogenesis was initiated in Wistar rats by intraperitoneal injections of azoxymethane (AOM), once a week for two weeks. One week after (post-initiation) rats received daily Asp (0.01%, 14 mg/kg body weight) in drinking water. After 7 weeks of Asp-treatment the colon of rats exhibited a 50% reduction of the number of preneoplastic lesions (aberrant crypt foci). In addition Asp induced inhibition of several pro-inflammatory mediators, in association with an increased expression of host-defense mediators. In the colonic mucosa of Asp-treated rats we also confirmed the pro-apoptotic effects observed in vitro including the activation of the TRAIL death‑receptor signaling pathway. Taken together, our data highlight the chemopreventive effects of Asp on colon carcinogenesis and its ability to promote normal cellular homeostasis. AD - University of Strasbourg, Unit EA 4438, Faculty of Medicine, Strasbourg, France AERIAL, Illkirch, France Max Rubner Institute, Karlsruhe, Germany University of Strasbourg, Faculty of Pharmacy, IPHC, CNRS-UMR7178, Illkirch, France Institut de Recherche contre les Cancers de l'Appareil Digestif (IRCAD), Strasbourg, France AU - Bousserouel,Souad AU - Le Grandois,Julie AU - Gossé,Francine AU - Werner,Dalal AU - Barth,Stephan ,W. AU - Marchioni,Eric AU - Marescaux,Jacques AU - Raul,Francis DA - 2013/08/01 DO - 10.3892/ijo.2013.1976 EP - 404 IS - 2 JO - Int J Oncol KW - Asparagus officinalis colorectal cancer SW480 cells SW620 cells aberrant crypt foci inflammation caspases death receptors PY - 2013 SN - 1019-6439 1791-2423 SP - 394 ST - Methanolic extract of white asparagus shoots activates TRAIL apoptotic death pathway in human cancer cells and inhibits colon carcinogenesis in a preclinical model T2 - International Journal of Oncology TI - Methanolic extract of white asparagus shoots activates TRAIL apoptotic death pathway in human cancer cells and inhibits colon carcinogenesis in a preclinical model UR - https://doi.org/10.3892/ijo.2013.1976 VL - 43 ER -