Schmutz Cornelia, Plaza Crepelle, Steiger Franziska, Stoirer Natascha, Gufler Judith, Pahlke Gudrun, Will Frank, Berger Walter, Marko Doris
Department of Food Chemistry and Toxicology, Faculty of Chemistry, University of Vienna, Währingerstraße 38-40, 1090 Vienna, Austria.
Doctoral School in Chemistry, University of Vienna, Währingerstraße 42, 1090 Vienna, Austria.
Antioxidants (Basel). 2024 Jul 15;13(7):846. doi: 10.3390/antiox13070846.
Chemotherapy with irinotecan (CPT-11), the pro-drug of the highly cytotoxic SN-38, is among the standard-of-care treatments for colorectal cancer. To counteract undesired toxic side effects on healthy tissue such as the intestinal epithelium, the use of preparations rich in polyphenols with anti-oxidative and anti-inflammatory properties such as anthocyanins has been proposed. In the present study, the question of whether non-tumorigenic human epithelium cells (HCEC-1CT) can be protected against the cytotoxic impact of SN-38 by anthocyanin-rich polyphenol extracts without compromising the desired therapeutic effect against tumor cells (HCT-116) was addressed. Hence, single and combinatory effects of anthocyanin-rich polyphenol extracts of elderberry (EB), bilberry (Bil), blackberry (BB) and black currant (BC) with the chemotherapeutic drug SN-38 were investigated. Out of the extracts, BB showed the most potent concentration-dependent cytotoxicity alone and in combination with SN-38, with even stronger effects in non-tumorigenic HCEC-1CT cells. In cytotoxic concentrations, BB decreased the level of DNA/topoisomerase I covalent complexes in HCEC-1CT cells below base level but without concomitant reduction in SN-38-induced DNA strand breaks. The herein reported data argue towards an interference of anthocyanins with successful treatment of cancer cells and a lack of protective properties in healthy cells.
伊立替康（CPT - 11）是高细胞毒性的SN - 38的前体药物，其化疗是结直肠癌的标准治疗方法之一。为了抵消对健康组织如肠上皮的不良毒副作用，有人提出使用富含具有抗氧化和抗炎特性的多酚（如花色苷）的制剂。在本研究中，探讨了非致瘤性人上皮细胞（HCEC - 1CT）是否能通过富含花色苷的多酚提取物免受SN - 38的细胞毒性影响，同时又不损害对肿瘤细胞（HCT - 116）的预期治疗效果。因此，研究了接骨木（EB）、越橘（Bil）、黑莓（BB）和黑加仑（BC）富含花色苷的多酚提取物与化疗药物SN - 38的单一和联合作用。在这些提取物中，BB单独使用以及与SN - 38联合使用时表现出最有效的浓度依赖性细胞毒性，在非致瘤性HCEC - 1CT细胞中的作用更强。在细胞毒性浓度下，BB可使HCEC - 1CT细胞中DNA/拓扑异构酶I共价复合物的水平降至基础水平以下，但不会同时降低SN - 38诱导的DNA链断裂。本文报道的数据表明花色苷会干扰癌细胞的成功治疗，且对健康细胞缺乏保护作用。
