title: Fatty Acid Composition of Tissue Cultured Breast Carcinoma and the Effect of Stearoyl-CoA Desaturase 1 Inhibition.
abstract: OBJECTIVE
  Stearoyl-CoA desaturase 1 (SCD1) is a novel therapeutic target in various malignancies, including breast cancer. The present study was designed to investigate the effect of the pharmacologic inhibition of SCD1 on fatty acid composition in tissue explant cultures of human breast cancer and to compare these effects with those in adjacent nonneoplastic breast tissue.
  
  
  METHODS
  Paired samples of tumor and adjacent noncancerous tissue were isolated from 12 patients with infiltrating ductal breast cancer. Samples were explant cultured in vitro, exposed to the highly selective SCD1 inhibitor CAY10566, and examined for fatty acid composition by gas liquid chromatography. The cytotoxic and antigrowth effects were evaluated by quantification of lactate dehydrogenase release and by sulforhodamine B (SRB) measurement, respectively.
  
  
  RESULTS
  Breast cancer tissue samples were found to have higher levels of monounsaturated fatty acids (MUFA) (p<0.001) and arachidonic acid (20:4n-6, p<0.001) and a lower level of linoleic acid (18:2n-6, p=0.02) than the normal-appearing breast tissues. While exhibiting no evident cytotoxicity, treatment with the SCD1 inhibitor, CAY10566 (0.1-1 µM), for 48 hours significantly increased 18:2n-6 levels in both the tumor and adjacent normal-appearing tissue (approximately 1.2 fold, p<0.05). However, the breast cancer tissue samples showed significant increases in the levels of MUFA and 20:4n-6 compared to the normal-appearing breast tissues (p<0.05). The SRB growth assay revealed a higher rate of inhibition with the SCD1 inhibitor in breast cancer tissues than in normal-appearing tissues (p<0.01, 41% vs. 29%). The SCD1 inhibitor also elevated saturated fatty acid (1.46-fold, p=0.001) levels only in the tumor tissue explant.
  
  
  CONCLUSIONS
  The fatty acid composition and response to SCD1 inhibition differed between the explant cultures from breast cancer and the adjacent normal-appearing tissue. Altered fatty acid composition induced by SCD1 inhibition may also, in addition to Δ9 desaturation, modulate other reactions in de novo fatty acid synthesis and lipogenesis, and subsequently affect the overall survival and progression of breast cancer.
authors.affiliation: Department of Biochemistry and Clinical Laboratories, Tabriz University of Medical Sciences School of Medicine, Tabriz, Iran.
authors.forename: Fatemeh
authors.initials: F
authors.lastname: Mohammadzadeh
authors.affiliation: Biotechnology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.
authors.forename: Gholamali
authors.initials: G
authors.lastname: Mosayebi
authors.affiliation: Department of Thoracic Surgery, Tabriz University of Medical Sciences, Tabriz, Iran.
authors.forename: Vahid
authors.initials: V
authors.lastname: Montazeri
authors.affiliation: Biotechnology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.
authors.forename: Maryam
authors.initials: M
authors.lastname: Darabi
authors.affiliation: Students Research Committee, Department of Anatomy and Cell Biology, Shahid Beheshti University of Medical Sciences School of Medicine, Tehran, Iran.
authors.forename: Shabnam
authors.initials: S
authors.lastname: Fayezi
authors.affiliation: Department of Biochemistry and Clinical Laboratories, Tabriz University of Medical Sciences School of Medicine, Tabriz, Iran.
authors.forename: Maghsod
authors.initials: M
authors.lastname: Shaaker
authors.affiliation: Department of Biochemistry and Clinical Laboratories, Tabriz University of Medical Sciences School of Medicine, Tabriz, Iran.
authors.forename: Mohammad
authors.initials: M
authors.lastname: Rahmati
authors.affiliation: Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.
authors.forename: Behzad
authors.initials: B
authors.lastname: Baradaran
authors.affiliation: Liver and Gastrointestinal Disease Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.
authors.forename: Amir
authors.initials: A
authors.lastname: Mehdizadeh
authors.affiliation: Biotechnology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.
authors.forename: Masoud
authors.initials: M
authors.lastname: Darabi
keywords: Breast neoplasms; Fatty acid desaturases; Tissue culture techniques