title: l-arginine alters the effect of 5-fluorouracil on breast cancer cells in favor of apoptosis.
abstract: Chemoresistance in breast cancer is a major obstacle, especially in p53 mutation types. The aim of this study was to evaluate if a combination therapy of l-arginine with 5-fluorouracil (5-FU) can alter the effect of this chemotherapy drug on breast cancer cells. The study was performed on BT-20 and MCF-7 cell lines. The effects of l-arginine alone and in combination with 5-FU were investigated on cell viability, apoptosis and nitric oxide (NO) production. Drugs effects on the cellular energetic metabolism were investigated through the lactate production and glucose-6-phosphate dehydrogenase (G6PD) activity assay. Migration and invasion of treated cells were assessed. Real- time PCR was used for analyzing the changes in the expression level of CXCL12 and CXCR4 as two important genes involved in migration and metastasis of breast cancer cells. l-arginine increased 5-FU effect on BT-20 and MCF-7 cell lines by reducing cell viability and increasing apoptosis and NO production. Lactate production and G6PD activity assays showed that cellular energetic metabolism of both cells was altered in favor of cell death. Moreover, l-arginine decreased the metastatic activity of both cells which was confirmed through migration, invasion and gene expression results performed for both cell lines. However, drugs effect on MCF-7 (p53 wild-type) was greater than that of BT-20 (p53 mutation) in all sets of experiments. Our findings indicated that l-arginine increased the anticancer effect of 5-FU in BT-20 and MCF-7 cell lines. So, combination therapy with l-arginine and 5-FU could be considered as an effective strategy in breast cancer therapy.
authors.affiliation: Medical Biology Research Center, Kermanshah University of Medical Sciences, Kermanshah, Iran.
authors.forename: Mozhgan
authors.initials: M
authors.lastname: Jahani
authors.affiliation: Department of Biology, Faculty of Basic Sciences, Razi University, Kermanshah, Iran.
authors.forename: Mehri
authors.initials: M
authors.lastname: Azadbakht
authors.affiliation: Medical Biology Research Center, Kermanshah University of Medical Sciences, Kermanshah, Iran.
authors.forename: Fatemeh
authors.initials: F
authors.lastname: Norooznezhad
authors.affiliation: Medical Biology Research Center, Kermanshah University of Medical Sciences, Kermanshah, Iran. Electronic address: kmansouri@kums.ac.ir.
authors.forename: Kamran
authors.initials: K
authors.lastname: Mansouri
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D001120:Arginine / Q000494:pharmacology*; D001943:Breast Neoplasms / Q000235:genetics / Q000473:pathology*; D002465:Cell Movement / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D054377:Chemokine CXCL12 / Q000235:genetics / Q000378:metabolism; D005260:Female; D005472:Fluorouracil / Q000494:pharmacology*; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D005954:Glucosephosphate Dehydrogenase / Q000378:metabolism; D006801:Humans; D019344:Lactic Acid / Q000096:biosynthesis; D061986:MCF-7 Cells; D008954:Models, Biological; D009361:Neoplasm Invasiveness; D009569:Nitric Oxide / Q000096:biosynthesis; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D019718:Receptors, CXCR4 / Q000235:genetics / Q000378:metabolism
chemical_list: C527276:CXCR4 protein, human; D054377:Chemokine CXCL12; D012333:RNA, Messenger; D019718:Receptors, CXCR4; D009569:Nitric Oxide; D019344:Lactic Acid; D001120:Arginine; D005954:Glucosephosphate Dehydrogenase; D005472:Fluorouracil
keywords: Apoptosis; Breast cancer; Metastasis; Nitric oxide