Emerging roles of lactic acid bacteria in protection against colorectal cancer

Figure 1 Potential mechanisms of action of lactic acid bacteria via extrinsic and intrinsic pathways of apoptosis[19,20]. The apoptosis signaling pathways can be activated by lactic acid bacteria (LAB) through the extrinsic and intrinsic pathways. The extrinsic pathway engages Fas/tumor necrosis factor receptors or other factors to induce caspase related pathway. The intrinsic pathway requires mitochondrial localization and activation of Bax and Bak that can be prevented by anti-apoptotic Bcl-2 family proteins or pharmacologic inhibitors. LAB enhanced the apoptosis induction capacity of 5-fluorouracil (5-FU) and induced the activation of autophagic cell death promoted directly by the induction of Beclin-1 and GRP78, as well as indirectly through the induction of Bcl-2 and Bak. LAB may act to prevent cancer via downregulating nuclear factor-kappaB (NF-κB)-dependent gene products which regulate cell proliferation (Cox-2, cyclin D1) and survival (Bcl-2, Bcl-xL).

Figure 2 Immune responses induced by lactic acid bacteria. Lactic acid bacteria (LAB) can provoke immune responses via two main pathways: inflammation and anticancer immune response. The inflammation pathways involve lipoteichoic acid (LTA) which can stimulate T cells to release interleukin (IL)-10, IL-12 and increase effectors Foxp3⁺RORγt^- Tregs. In the anticancer immune response pathway, LAB stimulate the immune cells, such as T cells, dendritic cell (DC), natural killer (NK) and MHC class II cells to induce IL-10, tumor necrosis factor (TNF)-α, interferon (IFN)-γ and IL-1β to inhibit tumor growth.