Chemoprevention by Microencapsulated Lactiplantibacillus Plantarum LAB12 Against Orthotopic Colorectal Cancer Mice is Associated with Apoptosis and Anti-angiogenesis.

Abstract

The pathogenesis of colorectal cancer (CRC) is associated with gut dysbiosis that is attributed to unhealthy lifestyles and dietary habits. Consumption of microencapsulated probiotics may potentially restore the gut microbiota in favour of prevention against CRC. This study determined the fate of microencapsulated Lactiplantibacillus plantarum (formerly known as Lactobacillus plantarum) LAB12 in the gastrointestinal tract (GIT) and assessed the chemopreventive effect of microencapsulated L. plantarum LAB12 in vivo. The targeted release of L. plantarum LAB12 from Alg-based microcapsules at the stomach, ileum, caecum and colon of Sprague-Dawley rats was examined by confocal microscopy and qPCR. Microcapsules loaded with L. plantarum LAB12 remained intact in the stomach. Free L. plantarum LAB12 were present in abundance (> 7 log CFU) only in the intestines. Subsequently, the chemopreventive properties of microencapsulated L. plantarum LAB12 were validated against NU/NU nude mice bearing orthotopic transplanted CT-26 CRC (12 female mice; 4-6weeks old; 20-22g; n = 6/group). Orthotopic mice pre-supplemented with microencapsulated L. plantarum LAB12 (10 log CFU kg-1 BW for 11weeks) were presented with significantly (p < 0.05) reduced tumour volume (- 98.87%) and weight (- 89.27%) when compared to control. Western blots indicated that the chemopreventive effect could be attributed to apoptosis and anti-angiogenesis mediated, at least in part, through upregulation of tumour suppressor p53 (+ 45.4%) and pro-apoptotic caspase-3 (+ 82.4%), and downregulation of pro-inflammatory COX-2 (- 57.9%), pro-angiogenic VEGF (- 66.8%) and PECAM-1 (-64.1%). Altogether, this study strongly implied the possibility of having L. plantarum LAB12-loaded microcapsules safely incorporated into food and nutraceutical products for prevention against CRC.