TY - JOUR
T1 - Fatty acid composition of tissue cultured breast carcinoma and the effect of stearoyl-CoA desaturase 1 inhibition
AU - Mohammadzadeh, Fatemeh
AU - Mosayebi, Gholamali
AU - Montazeri, Vahid
AU - Darabi, Maryam
AU - Fayezi, Shabnam
AU - Shaaker, Maghsod
AU - Rahmati, Mohammad
AU - Baradaran, Behzad
AU - Mehdizadeh, Amir
AU - Darabi, Masoud
PY - 2014/6
Y1 - 2014/6
N2 - 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 phar-macologic 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 quantifcation of lactate de-hydrogenase 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 ex-plant. 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 Δ9 desaturation, modulate other reactions in de novo fatty acid synthesis and lipogenesis, and subsequently affect the overall survival and progression of breast cancer.
AB - 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 phar-macologic 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 quantifcation of lactate de-hydrogenase 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 ex-plant. 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 Δ9 desaturation, modulate other reactions in de novo fatty acid synthesis and lipogenesis, and subsequently affect the overall survival and progression of breast cancer.
UR - http://www.scopus.com/inward/record.url?scp=84903989829&partnerID=8YFLogxK
U2 - 10.4048/jbc.2014.17.2.136
DO - 10.4048/jbc.2014.17.2.136
M3 - Journal articles
AN - SCOPUS:84903989829
SN - 1738-6756
VL - 17
SP - 136
EP - 142
JO - Journal of Breast Cancer
JF - Journal of Breast Cancer
IS - 2
ER -