Lactobacillus rhamnosus induced epithelial cell apoptosis, ameliorates inflammation and prevents colon cancer development in an animal model Yaser Gamallat a , Abdo Meyiah a , Eugene D. Kuugbee a , Ahmed Musa Hago b , Gift Chiwala a , Annoor Awadasseid a , Djibril Bamba a , Xin Zhang a , Xueqi Shang a , Fuwen Luo c, **, Yi Xin a, * a Department of Biochemistry and Molecular Biology, Dalian Medical University, Dalian 116044, China b Department of Pathology and Pathophysiology, Dalian Medical University, Dalian 116044, China c Department of Acute abdominal Surgery, Second Affiliated Hospital of Dalian Medical University, China A R T I C L E I N F O Article history: Received 1 May 2016 Received in revised form 14 June 2016 Accepted 1 July 2016 Keywords: Colon cancer Lactobacillus Apoptosis Inflammation A B S T R A C T Background/Aim: Probiotics have been suggested as prophylactic measure in colon carcinogenesis. This study aimed at determining the potential prophylactic activity of Lactobacillus rhamnosus GG CGMCC 1.2134 (LGG) strain on colorectal carcinogenesis via measuring its effect on Nuclear factor kappa B (NFkB) inflammatory pathway and apoptosis. Materials and methods: 64 Sprague Dawley rats were grouped into four as follows; Group 1 (Healthy control), Group 2 (LGG), Group 3 (cancer control Dimethyl hydrazine (DMH)) and Group 4 (LGG + DMH). LGG was administered orally to LGG and LGG + DMH groups. Colon carcinogenesis was chemically induced in LGG + DMH and DMH groups by weekly injection of 40 mg/kg DMH. Animals were sacrificed after 25 weeks of experiment and tumor characteristics assessed. The change in expression of NFkB-p65, COX-2, TNFa, Bcl-2, Bax, iNOS, VEGFa, b-catenin, Casp3 and p53 were evaluated by western blotting and qRT-PCR. Results: LGG treatment significantly reduced tumor incidence, multiplicity and volume in LGG + DMH treatment group compared to DMH cancer control group. Also, LGG treatment reduced the expression of b-catenin and the inflammatory proteins NFkB-p65, COX-2 and TNFa; the anti-apoptotic protein Bcl-2, but increased the expression of the pro-apoptotic proteins Bax, casp3 and p53 compared with DMH group. Conclusion: LGG have a potential protection effect against colon carcinogenesis; inducing apoptosis and ameliorating inflammation, and may hold a promise as bio-therapeutic dietary agent. ã 2016 Elsevier Masson SAS. All rights reserved. 1. Introduction Colorectal cancer is the third most common cause of cancer related deaths in developed countries with more than a million new cases each year [1]. A recent study by Chen et al. [2] indicates that China alone registered 2.8 million deaths with 4.3 million new cases of cancer in 2015. While systems are working around the clock to find a lasting solution to cancer, the challenge still lies in the inability to identify new treatment strategies beyond chemotherapy to inhibit tumor progression. Probiotics, which include lactic acid bacteria, have health benefits when applied in proper dose and have been proven to possess prophylactic functions such as improved nutrition, microbial balance and immuno-enhancement of the gastrointesti- nal tract (GIT) [3–5]. Probiotics have been used for the prevention and treatment of a wide range of disorders from gastroenteritis to intestinal neoplasia. The well-known benefits of probiotics’ use in the management of antibiotic associated diarrhea lies in restora- tion of the normal microbiota [6]. However, the mechanisms of probiotics efficacy in many disorders are not well established. Probiotic-therapy has been explored in non-gastrointestinal diseases like the treatment and prevention of atopic eczema [7]. Nevertheless, the evidence to date suggests that the major clinical effects of probiotics are seen in GIT disorders. Animal model experiments have shown that the intestinal microbiota is important in stimulating normal immune system development, * Corresponding author. ** Co-corresponding author. E-mail addresses: fuwenluo@aliyun.com (F. Luo), jimxin@hotmail.com (Y. Xin). http://dx.doi.org/10.1016/j.biopha.2016.07.001 0753-3322/ã 2016 Elsevier Masson SAS. All rights reserved. Biomedicine & Pharmacotherapy 83 (2016) 536–541 Available online at ScienceDirect www.sciencedirect.com