Premium
Arginase Inhibition Suppresses Breast Cancer Cell Proliferation
Author(s) -
Shatanawi Alia,
Qasrawi Heba
Publication year - 2017
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.31.1_supplement.lb529
Subject(s) - arginase , spermidine , ornithine decarboxylase , spermine , cell growth , cancer cell , ornithine , chemistry , cancer research , polyamine , cancer , breast cancer , enzyme , biology , biochemistry , arginine , medicine , amino acid
Breast cancer is the second most common cause of cancer worldwide. It is recognized to be the most common cancer in women. It is also considered as the second leading cause of cancer death in women in the United States. There is accumulating evidence of increased arginase activity in patients with breast cancer. Arginase, an enzyme of the urea cycle, catalyzes the hydrolysis of L‐arginine to urea and L‐ornithine. L‐ornithine is converted to polyamines by the enzyme ornithine decarboxylase (ODC). Polyamines such as spermidine and spermine have an important role in cell proliferation. Hence, polyamines are also found to have an important role in tumor development and growth. Levels of polyamines are found to be 2–3 times higher in breast cancer cells than in normal surrounding tissue. We studied the effects of arginase inhibition on breast cancer cells and endothelial cells in vitro . Our experiments utilized MCF‐7 breast cancer cells or bovine aortic endothelial cells. Arginase activity was measured in cells treated with or without the novel arginase inhibitor; 2(S)‐amino‐6‐boronohexanoic acid (ABH). Additionally, the effect of ABH treatment on cells proliferation in vitro was determined using cell proliferation assay. Our results show that arginase inhibition caused a concentration dependent suppression of MCF‐7 cell proliferation with a maximum inhibitory concentration of 500 μM. This dose of ABH resulted in a 30% decrease in cell proliferation versus untreated controls. Arginase activity was measured in cells treated with ABH and was decreased by 60% versus controls. Interestingly, while ABH inhibited arginase activity in endothelial cells, it did not have any effect on the proliferation rate of endothelial cells. Our results indicate that arginase can be considered a new therapeutic target for suppressing breast cancer cell growth. Arginase inhibitors represent a potential cancer therapy in tumors with elevated arginase activity. Support or Funding Information The University of Jordan Deanship of Research