Berries and leukemia: a systematic review of experimental studies and the in vitro effect of ellagic acid on chronic myeloid leukemia cells

Abstract

Diet is directly involved in cancer etiology, influencing positively or negatively. The aim of this study was to conduct a systematic review on the effect of berries on leukemia, identifying the main bioactive compounds involved in biochemical and molecular mechanisms through which they act and also to test the in vitro effect of ellagic acid, one of the phytochemicals found in berries, on leukemia cells. The work was subdivided into two parts: the first consisted of analysis of abstracts in Pubmed / Medline databases using MeSH (Medical Subject Headings) terms, synonyms, related and free terms, such as: leukemia, berries, anthocyanins, ellagic acid and flavonoids resulting in 274 articles. After abstract analysis, based on the eligibility criteria, this number was reduced to 21 articles. The second part was the in vitro investigation of the effect of ellagic acid by the MTT reduction in chronic myeloid leukemia cell lines (CML) resistant or not to chemotherapeutic agents. In vitro , in vivo and ex vivo studies associated the bioactive compounds present in berries with anticancer effect, acting mainly by induction of metabolic enzymes, modulation of gene expression and cell proliferation, chemotherapic resistance, free radical scavenging and induction of apoptosis. The present work also highlights the induction of collateral sensitivity by ellagic acid, since this compound was able to preferentially act on chemotherapeutic resistant cells. However, it is emphasized that animal models and clinical trials are for establishing the main mechanisms of action and possible dosages of berries intake daily or by dietary supplementation that could contribute to leukemia's treatment.