P12-22 Anthocyanin-rich elderberry extract during chemotherapy: Berry good or berry bad?

Berry products rich in anthocyanins are widely recognized for their health benefits and are increasingly discussed for their potential to mitigate adverse effects of chemotherapy. Colorectal cancer, the third most common cancer worldwide, is frequently treated with the topoisomerase I inhibitor prodrug irinotecan as a first- or second-line therapy. A prevalent side effect of irinotecan and its active metabolite SN38 is diarrhea due to damage to the intestinal epithelium. Anthocyanins are hypothesized to counteract this damage due to their antioxidative, anti-inflammatory, and topoisomerase I-modulating properties in the gastrointestinal tract. This study assessed the potential of anthocyanin-rich elderberry extracts to reduce irinotecan-induced damage on the intestinal tissue without compromising its anticancer efficacy in mice. Anthocyanin-rich elderberry extract (EB) was administered alongside irinotecan to CT26 tumor-bearing immunocompetent (Balb/c) and immunodeficient (SCID) mice over two weeks. Tumor growth and topoisomerase/DNA complex formation in tumor and colon tissues revealed differential interactions between EB and irinotecan in the two mouse strains. While EB augmented the activity of irinotecan in immunodeficient mice, tumor growth in immunocompetent mice was markedly increased in the combination compared to irinotecan alone. Regarding side effects, body weight remained widely unaffected by the treatment. However, marker expressions in various organs suggested a possible exacerbation of irinotecan-induced adverse effects by EB in immunocompetent mice. Additionally, LC-MS/MS analysis of urine, plasma and feces will shed light on the effect of EB on irinotecan metabolism and excretion. In conclusion, EB influenced both the efficacy and side effects of irinotecan, dependent on the immune status of mice. These findings underscore the importance of considering immune status in future combination studies, which frequently utilize immunodeficient mice, and in dietary recommendations for patients undergoing chemotherapy. Funding: This work was partially funded by the Austrian Science Fund (FWF) ESP87 and P31805