Newly Obtained Apple Pectin as an Adjunct to Irinotecan Therapy of Colorectal Cancer Reducing E. coli Adherence and β-Glucuronidase Activity

SIMPLE SUMMARY: Colorectal cancer (CRC) is the second cause of cancer death worldwide. Irinotecan is a drug widely used in CRC treatment. Unfortunately, colonic bacteria decompose the metabolite of irinotecan back to the active form of the drug resulting in severe side-effects of the treatment, such as diarrhea. The present work demonstrated that new apple pectin (PC) enhanced cytostatic action of irinotecan and, at the same time, reduced the activity of bacterial enzymes responsible for the appearance of side-effects in patients. Thus, novel pectin PC constitutes a promising candidate for an adjunct to irinotecan therapy that might alleviate its side-effects, increasing its therapeutic efficacy. 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 IC(50)), 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-12(C600) 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.