Abstract
Colorectal cancer (CRC) is the second cause of cancer death worldwide. The composition and enzymatic activity of colonic microbiota can significantly affect the effectiveness of CRC chemotherapy. Irinotecan is a drug widely used to treat colon cancer. However, the transformation of a drug-glucuronide (SN-38G) back to its active form (SN-38) by bacterial β-glucuronidase (GUS) constitutes the primary reason for the observed intestinal toxicity of irinotecan. It was demonstrated that novel enzymatically extracted apple pectin (PC) might be a promising candidate for an adjunct to irinotecan therapy. PC itself reduced the viability of HCT 116 and Caco-2 colorectal cancer cells, induced apoptosis, and increased intracellular reactive oxygen species production. Moreover, PC enhanced the cytotoxic and proapoptotic effect of irinotecan (at concentrations below its IC50), i.e., synergistic effect was recorded. Additionally, PC exhibited potent anti-inflammatory properties and prevented adhesion of prototype adherent-invasive E. coli (AIEC) LF82 strain and laboratory K-12C600 strain to colon cancer cells. PC was also identified to be an effective inhibitor of bacterial GUS activity. Altogether, novel apple pectin was identified as a promising candidate for a supplement to irinotecan therapy that might alleviate its side-effects via inhibition of bacterial GUS and thus increasing its therapeutic efficacy.