A research team has used genetic engineering to transform a harmless bacteria found in the gut into a probiotic that targets and kills colorectal cancer cells. The engineered microbes secrete the enzyme, myrosinase, which transforms a natural component of cruciferous vegetables into an anticancer compound. In advanced stages, colorectal cancer tends to often reappear and the survival rate for individuals is low. The study findings are published in the journal, Nature Biomedical Engineering.
In the study, genetically engineered E. coli Nissle attached to the surface of colorectal cancer cells and used myrosinase to transform glucosinolates, naturally found in broccoli and other cruciferous vegetables, to the small molecule, sulphorophane, which is known to have anticancer properties. The in vitro study results showed there was greater than 95% proliferation inhibition in murine and human colorectal adenocarcinoma cell lines. Importantly, non-cancerous cells were not impacted by the treatment because they cannot perform the same enzymatic conversion as the engineered probiotic. In vivo treatments showed significant reduction in the number and size of tumors in murine mouse models with colorectal cancer.
The research team envisions these probiotics to be used for prevention of colorectal cancer and to potentially help remove any leftover cancer cells after tumor extraction. Associate Professor Chang from the National University Hospital remarks, "One exciting aspect of our strategy is that it just capitalizes on our lifestyle, potentially transforming our normal diet into a sustainable, low-cost therapeutic regimen. We hope that our strategy can be a useful complement to current cancer therapies."
Orally administered engineered microbes bind to the surfaces of colorectal cancer cells (a), allowing microbes to secrete myrosinase, which converts dietary glucosinolate found in cruciferous vegetables (b). When the cancer cells are cleared, the microbes are released from the surface of the intestinal wall (c).
Image Credit: Ho CL, Tan HQ, Chua KJ, Kang A, Lim KH, Ling KL, et al. Engineered commensal microbes for diet-mediated colorectal-cancer chemoprevention. Nat Biomed Eng. Jan 2018.