Fatty Acid Composition of Tissue Cultured Breast Carcinoma and the Effect of Stearoyl-CoA Desaturase 1 Inhibition
Journal of Breast Cancer 2014³â 17±Ç 2È£ p.136 ~ p.142
(Mohammadzadeh Fatemeh) - Tabriz University of Medical Sciences School of Medicine Department of Biochemistry and Clinical Laboratories
(Mosayebi Gholamali) - Tabriz University of Medical Sciences Biotechnology Research Center
(Montazeri Vahid) - Tabriz University of Medical Sciences Department of Thoracic Surgery
(Darabi Maryam) - Tabriz University of Medical Sciences Biotechnology Research Center
(Fayezi Shabnam) - Shahid Beheshti University of Medical Sciences School of Medicine Department of Anatomy and Cell Biology
(Shaaker Maghsod) - Tabriz University of Medical Sciences School of Medicine Department of Biochemistry and Clinical Laboratories
(Rahmati Mohammad) - Tabriz University of Medical Sciences School of Medicine Department of Biochemistry and Clinical Laboratories
(Baradaran Behzad) - Tabriz University of Medical Sciences Immunology Research Center
(Mehdizadeh Amir) - Tabriz University of Medical Sciences Liver and Gastrointestinal Disease Research Center
(Darabi Masoud) - Tabriz University of Medical Sciences Biotechnology Research Center
Abstract
Purpose: 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 ¥ìM), 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.
Conclusion: 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 ¥Ä9 desaturation, modulate other reactions in de novo fatty acid synthesis and lipogenesis, and subsequently affect the overall survival and progression of breast cancer.
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Breast neoplasms, Fatty acid desaturases, Tissue culture techniques
KMID :
1134120140170020136
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