Darabi, M.

Fayezi, S.

Mehdizadeh, A.

Mohammadzadeh, F.

Mosayebi, G.

Shaaker, M.

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Preclinical breast cancer biology63P FATTY ACID COMPOSITION OF TISSUE CULTURED BREASTCARCINOMA: EFFECTOF STEAROYL-COA DESATURASE-1(SCD-1) INHIBITORM. Darabi1, F. Mohammadzadeh2, M. Darabi3, S. Fayezi4, G. Mosayebi3,M. Shaaker3, A. Mehdizadeh21University of Zurich, Institute of Clinical Chemistry, Zurich, SWITZERLAND2Tabriz University of Medical Sciences, Biotechnology Research Center, Tabriz,IRAN3Tabriz University of Medical Sciences, Department of Biochemistry and ClinicalLaboratories, Tabriz, IRAN4Student Research Committee and Department of Anatomy and Cell Biology,Shahid Beheshti University of Medical Sciences, Tehran, IRANIntroduction: Stearoyl-CoA desaturase 1 (SCD1) has been introduced as a noveltherapeutic target in malignancies, including breast cancer. The present study wasdesigned to investigate the effect of pharmacologic inhibition of SCD1 on fatty acidprofile in tissue explant culture of human breast cancer, and also to compare theseeffects with those in adjacent non-neoplastic breast tissue.Methods: Paired samples of tumor and adjacent non-cancerous tissue were isolatedfrom twelve patients with infiltrating ductal breast cancer, explant cultured in vitro,exposed to a highly selective SCD1 inhibitor CAY10566, and investigated with respectto fatty acid composition by gas liquid chromatography (GLC). Anti-proliferative andcytotoxic effects were evaluated by quantification of lactate dehydrogenase (LDH)release and by sulforhodamine B (SRB) measurement.Results: In the breast cancer tissue, levels of monounsaturated fatty acids (MUFA,P < 0.001) and arachidonic acid (20:4n-6; P < 0.001) were higher, and the level oflinoleic acid (18:2n-6; P = 0.02) was lower than that in the normal-appearing breast.While exhibiting no evident cytotoxicity, treatment with SCD1 inhibitor (0.1-1 µM) for48 hours significantly increased linoleic acid (18:2n-6) in both tumor and adjacentnormal tissue (≃1.2 fold, P < 0.05). However, the levels of MUFA and 20:4n-6, and theratio of oleic acid (18:1n-9) to stearic acid (18:0) showed larger fold changes in thebreast cancer than in normal-appearing breast (P = 0.02). SCD1 inhibitor alsorepressed growth/proliferation (≃50%, P = 0.001) and elevated SFA (1.4-fold,P = 0.001) level only in the tumor tissue explant.Conclusion: There were differences in the fatty acid composition and response toSCD1 inhibition between the explant cultures from breast cancer compared to adjacentnon-neoplastic tissue. Altered fatty acid composition induced by SCD1 inhibition maymodulate other reactions in de novo fatty acid synthesis, lipogenesis and subsequentlyoverall breast cancer survival and progression.Disclosure: All authors have declared no conflicts of interest.© European Society for Medical Oncology 2014. Published by Oxford University Press on behalf of the European Society for Medical Oncology.All rights reserved. For permissions, please email: journals.permissions@oup.com.abstractsAnnals of Oncology 25 (Supplement 1): i21–i22, 2014doi:10.1093/annonc/mdu069.5

63PFATTY ACID COMPOSITION OF TISSUE CULTURED BREAST CARCINOMA: EFFECT OF STEAROYL-COA DESATURASE-1 (SCD-1) INHIBITOR

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