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

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-glucuronid...

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Bibliographic Details
Published in:Cancers 2021-06, Vol.13 (12), p.2952
Main Authors: Palko-Łabuz, Anna, Maksymowicz, Jerzy, Sobieszczańska, Beata, Wikiera, Agnieszka, Skonieczna, Magdalena, Wesołowska, Olga, Środa-Pomianek, Kamila
Format: Article
Language:English
Subjects:
Anti-inflammatory agents
Apoptosis
Bacteria
Cancer therapies
Cell cycle
Cellulase
Chemotherapy
Colon cancer
Colorectal cancer
Colorectal carcinoma
Cytotoxicity
Diarrhea
Drug dosages
Enzymatic activity
Enzymes
Experiments
Flow cytometry
Inflammation
Invasiveness
Irinotecan
Microbiota
Pectin
Reactive oxygen species
Side effects
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Summary: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.
ISSN:2072-6694
2072-6694
DOI:10.3390/cancers13122952