Appraisal of the anti-cancer potential of probiotic Pediococcus pentosaceus GS4 against colon cancer: in vitro and in vivo approaches Vinay Dubey a , Asit Ranjan Ghosh a, *, Kausik Bishayee b , Anisur Rahman Khuda-Bukhsh b a Centre for Infectious Diseases & Control, School of Bioscience and Technology,VIT University,Vellore 632014, India b Cytogenetics and Molecular Biology Laboratory, Department of Zoology, University of Kalyani, District Nadia, Kalyani, West Bengal 741235, India ARTICLE INFO Article history: Received 21 December 2015 Received in revised form 15 February 2016 Accepted 16 February 2016 Available online ABSTRACT Probiotic Pediococcus pentosaceus GS4 produces conjugated linoleic acid (CLA) through biohydrogenation, which may be vital for colon cancer mitigation. Here, we have ap- praised the anti-cancer potential of probiotic GS4 against colon cancer. CLA produced by probiotic GS4 reduced the proliferation of HCT-116 in vitro rendering towards apoptosis and subsequently abrogated NF-κB and p-Akt. Probiotic GS4 efficiently mitigated colon cancer in azoxymethane (AOM)-induced colon cancer mice model, which was evident from reduced disease severity, alleviated oxidative stress and neoplastic characters. Further delineation of underlying consequences at the level of host–microbe interface, the probiotic GS4 arbi- trated the gut microflora-associated biohydrogenation, which subsequently triggered apoptosis in colonocytes, apparent from PARP cleavage, caspase 3 activity, DNA fragmentation and inhibition of HDAC activity. Conclusively, modulation of host–microbe interface with selec- tive colonizing strategies combined with unique biohydrogenation ability of probiotic GS4 promises to be a therapeutic/functional food supplement responsible for mitigation of colon cancer. © 2016 Elsevier Ltd. All rights reserved. Keywords: Colon cancer Probiotic Biohydrogenation Conjugated linoleic acid Apoptosis 1. Introduction Colon cancer is increasing to a pandemic scale and is accom- panied by subsequent morbidity and mortality (SEER Stat Fact Sheet, 2015). Although there have been noteworthy achieve- ments in the therapeutic strategies in recent years, the treatment of colon cancer still remains a formidable task. Che- motherapeutic nonsteroidal anti-inflammatory drugs (NSAIDs) are the first line of therapy used with significant relief to the patients (Ahnen, 1998). However, NSAIDs like Troglitazone (Rezulin), Rofecoxib and Lumiracoxib have been withdrawn from the market due to their severe side-effects such as liver injury and heart stroke (Qureshi, Seoane-Vazquez, Rodriguez-Monguio, Stevenson, & Szeinbach, 2011). Therefore, there is a dire need for a safer anti-cancer agent with anti-inflammatory properties. Much data suggest that the alterations in gut microflora can be considered as an aetiological factor in colon cancer * Corresponding author. Centre for Infectious Diseases & Control, School of Bio Sciences and Technology,VIT University,Vellore 632014, India. Tel.: +91 9790238701; fax: +91 4162243092. E-mail addresses: asitranjanghosh@vit.ac.in; cidcvit@gmail.com (A.R. Ghosh). http://dx.doi.org/10.1016/j.jff.2016.02.032 1756-4646/© 2016 Elsevier Ltd. All rights reserved. Journal of Functional Foods 23 (2016) 66–79 Available online at www.sciencedirect.com journal homepage: www.elsevier.com/locate/jff ScienceDirect