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

Cancers

Olga Wesołowska¹  Kamila Środa-Pomianek¹  Jerzy Maksymowicz¹  Anna Palko-Łabuz¹  Agnieszka Wikiera²  Beata Sobieszczańska³  Magdalena Skonieczna⁴ 

[1] Department of Biophysics and Neuroscience, Wroclaw Medical University, 50-368 Wroclaw, Poland;Department of Biotechnology and General Technology of Foods, Faculty of Food Technology, University of Agriculture in Krakow, 30-149 Krakow, Poland;Department of Microbiology, Wroclaw Medical University, 50-368 Wrocław, Poland;Department of Systems Biology and Engineering, The Silesian University of Technology, 44-100 Gliwice, Poland;

关键词: colon cancer;    pectin;    irinotecan;    apoptosis;    inflammation;    E. coli;   

DOI  :  10.3390/cancers13122952

来源: DOAJ

【 摘 要 】

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-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.

【 授权许可】

Unknown