L-arginine/5-fluorouracil combination treatment approaches cells selectively: Rescuing endothelial cells while killing MDA-MB-468 breast cancer cells.

L-arginine/5-fluorouracil combination treatment approaches cells selectively: Rescuing endothelial cells while killing MDA-MB-468 breast cancer cells. Food Chem Toxicol. 2018 Nov 10;: Authors: Jahani M, Azadbakht M, Rasouli H, Yarani R, Rezazadeh D, Salari N, Mansouri K Abstract Reducing the adverse effects of chemotherapy on normal cells such as endothelial cells is a determinant factor of treatment success especially in pregnant women. In this regard, modulatory effect of L-arginine on various cancers is still a controversial topic in cancer therapy. So, this study aimed to compare the effect of L-arginine treatment alone and in combination with 5-fluorouracil (5-FU) on the survival and angiogenesis of primary human umbilical vein endothelial cells (HUVECs) and the breast cancer cell line of MDA-MB-468. Combinations of L-arginine and 5-FU increased cell survival in HUVECs but induced cell death in MDA-MB-468 cells. Nitric oxide assay showed an increase of this molecule in both cell lines. Assessments of metabolic changes as well as molecular docking indicated a decrease in glycolytic activity of cancer cells but not normal cells. Angiogenesis induction in HUVECs was confirmed through VEGF and MMP-2,9 up-regulated gene expressions. However, a down-regulation of the above-mentioned genes expression was observed in MDA-MB-468. Furthermore, an in vivo increased angiogenesis and decreased embryo toxicity was observed in combination tr...
Source: Food and Chemical Toxicology - Category: Food Science Authors: Tags: Food Chem Toxicol Source Type: research