Catechin complexed with lysine has potent antitumor activities in human breast cancer xenograft model

Abstract

AimsMitochondrially-produced superoxide anion has been recently recognized as a factor responsible for metastasis induction and development of secondary tumor lesions. Certain polyphenols, such as catechins, have strong antioxidant properties that may be exerted specifically at the intracellular site of superoxide production and have been proved to be effective against the development and progression of various cancer types. The purpose of this work was the evaluation of the protective activities of a novel antioxidant conjugate of (+)-cathechin:lysine 1:2 against the metastatic phenotype of breast cancer cells.MethodsWe utilized standard toxicity and viability assays to determine the anticancer activity of the complex in vitro in various cancerous cell lines, with emphasis given on the human breast cancer cell line MDA-MB231. The implicated protective mechanisms of (+)-cathechin:lysine 1:2 against MDA-MB231 cell migration and invasion were studied using expression analysis of certain metastatic (epithelial-mesenchymal transition; EMT) and proliferation markers. The possibility of the complex to protect against breast cancer progression in vivo was investigated using a xenograft model of immunocompromised mice generated by orthotopic implantation of GFP-tagged MDA-MB231 cells.ResultsWe determined that the action of (+)-cathechin:lysine 1:2 in vitro was time- and dose- dependent, and identified a sublethal concentration which was able to potently inhibition breast cancer migration and invasion by over 50%. These effects were notably accompanied by differences in expression of proliferation (p38), DNA-repair (p53), EMT (pyk2/SNAIL) and endoplasmic reticulum stress (GRP78) markers. In vivo, the complex was found to similarly affect primary tumors but not to inhibit metastasis incidence to lungs.ConclusionOur results suggest that the antioxidant action of (+)-cathechin:lysine 1:2 complex may exert protective effects against breast cancer progression in xenograft models and that further experiments are required to assess its efficacy in combination with other widely used treatments in clinic. Of note, manipulation of p53-dependent pathways may account for its anticancer potency.CommentsThis work was performed in Universite Catholique de Louvain Medical School, where the authors were occupied as postdocs in the lab of Pierre Sonveaux. The project was supervised by P. Sonveaux, but due to conflicts of interests, he is not placed as an author. However, the official publication and distribution of the current work is on P. Sonveaux’ discretion and judgement. We do acknowledge P. Niebes and H. May for the provision of the Catechin:lysine 1:2 complex.