Abstract
Abstract Colorectal cancer (CRC), also known as colon/bowel cancer, is the third most commonly diagnosed cancer in the world. In the United States, 142,820 new cases of CRC and 50,830 CRC-related deaths are predicted for the year 2013. CRC has been widely associated with lifestyle and aging. Treatment for CRC varies greatly based on disease severity and is curable with surgery, only if detected very early. It is being increasingly appreciated that nutritional and lifestyle modification might prevent or delay certain cancers, including CRC. Imbalance in gut microbiome, due to lifestyle and dietary habits, can lead to a variety of intestinal disorders including excessive immune response and inflammation that might ultimately lead to CRC. The probiotics, which are live microorganisms, have been shown to promote healthy microbiome balance in gut to support healthy colon. For an optimal functioning, the probiotics need to remain viable. This might be achieved via prebiotics and prebiotics-like substances that confer beneficial effects by promoting the microbiota. Therefore, novel means to balance the gut microbiota by prebiotic-probiotic combination could be useful in the management of inflammation related CRC. The grape antioxidant resveratrol (RSV) has been shown to support the health of beneficial gut bacteria, thus functioning essentially as a prebiotic. The goal of this study was to determine if a combination of the resveratrol and the probiotic Lactobacillus rhamnosus GG (LGG) imparts anti-proliferative response in human CRC cell lines, DLD 1 and RKO. For our experiments, DLD1 and RKO cells (∼50% confluent) were treated with RSV and cell free supernatants of LGG. RSV was used at a single concentration (10 µM) whereas LGG cell-free supernatants were used at two concentrations: LGG1 (2.125 x 105 CFU/mL) and LGG2 (4.35 x 105 CFU/mL). We found that a combination of LGG and RSV resulted in a significant decrease in the growth and viability of DLD 1 and RKO cells, as assessed by MTT- and Trypan Blue exclusion- assays. Further, LGG-RSV combination resulted in a marked decrease in the clonogenic survival of CRC cells, as assessed by colony formation abilities of of DLD 1 and RKO cells. Furthermore, LGG-RSV combination resulted in an induction of apoptosis in CRC cells, as determined by cleavage of protein poly (ADP-ribose) polymerase (PARP). Overall, our study provides a proof of principle for the potential use of RSV-LGG combination in CRC management. However, further in vivo studies in appropriate animal model(s) are needed to determine the efficacy of RSV-LGG combination in prevention of CRC. Citation Format: Chandra K. Singh, Jasmine George, Megan Duster, Nasia Safdar, Nihal Ahmad. Combination of the probiotic Lactobacillus rhamnosus GG with grape antioxidant resveratrol for the management of colorectal cancer. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 235. doi:10.1158/1538-7445.AM2014-235
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