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.

中文翻译：

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新获得的苹果果胶作为伊立替康治疗结肠直肠癌的辅助剂，可降低大肠杆菌粘附和 β-葡萄糖醛酸酶活性。

结直肠癌 (CRC) 是全球癌症死亡的第二大原因。结肠微生物群的组成和酶活性可以显着影响结直肠癌化疗的有效性。伊立替康是一种广泛用于治疗结肠癌的药物。然而，药物-葡萄糖醛酸苷 (SN-38G) 被细菌 β-葡萄糖醛酸苷酶 (GUS) 转化回其活性形式 (SN-38) 是观察到的伊立替康肠道毒性的主要原因。结果表明，新型酶法提取的苹果果胶 (PC) 可能是伊立替康治疗的辅助药物。PC 本身降低了 HCT 116 和 Caco-2 结肠直肠癌细胞的活力，诱导细胞凋亡，并增加了细胞内活性氧的产生。而且，PC 增强了伊立替康的细胞毒性和促凋亡作用（在低于其 IC50 的浓度下），即记录到协同作用。此外，PC 表现出有效的抗炎特性，并防止原型粘附侵入性大肠杆菌 (AIEC) LF82 菌株和实验室 K-12C600 菌株与结肠癌细胞的粘附。PC 也被鉴定为细菌 GUS 活性的有效抑制剂。总而言之，新型苹果果胶被确定为伊立替康治疗补充剂的有希望的候选者，可以通过抑制细菌 GUS 来减轻其副作用，从而提高其治疗效果。大肠杆菌 (AIEC) LF82 菌株和实验室 K-12C600 菌株对结肠癌细胞的影响。PC 也被鉴定为细菌 GUS 活性的有效抑制剂。总而言之，新型苹果果胶被确定为伊立替康治疗补充剂的有希望的候选者，可以通过抑制细菌 GUS 来减轻其副作用，从而提高其治疗效果。大肠杆菌 (AIEC) LF82 菌株和实验室 K-12C600 菌株对结肠癌细胞的影响。PC 也被鉴定为细菌 GUS 活性的有效抑制剂。总而言之，新型苹果果胶被确定为伊立替康治疗补充剂的有希望的候选者，可以通过抑制细菌 GUS 来减轻其副作用，从而提高其治疗效果。