Critical aspects in the use of polyphenol‐enriched preparations

Colorectal cancer (CRC) represent the third most frequent cancer in western countries.Chemotherapeutic treatment schemes often comprise the topoisomerase poison irinotecan .Topoisomerase poisons stabilize the covalent DNAtopoisomerase intermediate, which is formed during the catalytic cycle of topoisomerases to regulate torsion stress in the DNA and enable crucial processes such as DNA transcription, replication and repair.In proliferating cells, stabilisation of the DNA-topoisomerase intermediates leads to collision of these complexes with the replication fork and DNA damage.As a negative side effect, also non-tumorigenic proliferative tissue such as the intestinal epithelium can be impaired.In vitro studies identified anthocyanins as potential catalytic topoisomerase inhibitors.Catalytic topoisomerase inhibitors prevent the enzyme from the formation of covalent DNA complexes, thus diminishing the toxic impact of therapeutic topoisomerase poisons.Thus, the question arises whether anthocyanin-rich preparations might be used to protect the intestinal tissue without compromising the therapeutic outcome.Several berry species such as bilberry, blackberry, elderberry and black currant are known as rich sources for anthocyanins, but differ substantially in their respective anthocyanin profile.Within the huge class of polyphenols, anthocyanins possess unique structural elements, requiring a low pH to ensure respective stability.To overcome this problem, anthocyanin-rich preparations are usually acidified prior to application in vivo.One possibility is the acidification with citric acid, an often used strategy in studies comprising anthocyanins.Indeed, in BALB/C mice, the systemic bioavailability of anthocyanins was clearly enhanced by oral application of anthocyanin-rich extracts in citric acid compared to sodium chloride solution.However, in the present study we clearly demonstrated that the application of citric acid to tumor-bearing (CT26 murine colon carcinoma) BALB/C mice stabilized co-applied anthocyanins but citric acid per se strongly suppressed tumor growth.However, the application of the blackberry extract was not well tolerated by the animals and substantial toxicity was observed irrespective of application of the extract in citric acid or sodium chloride solution.These results question a potential health benefit of blackberry-based preparations as food supplements.Taken together, the study underlines the potential of polyphenol-rich food supplements to interfere with chemotherapeutic cancer treatment and the necessity to eventually prevent respective consumption in patients.