Abstract 236: Stearoyl-CoA desaturase-1, a novel target of omega-3 fatty acids for reducing breast cancer risk in obese postmenopausal women

• Published in: Cancer research (Chicago, Ill.) Vol. 77; no. 13_Supplement; p. 236
• Main Authors: Manni, Andrea, Richie, John P., Schetter, Susann E., Calcagnotto, Ana, Trushin, Neil, Aliaga, Cesar, El-Bayoumy, Karam
• Format: Journal Article
• Language: English
• Published: 01.07.2017
• ISSN: 0008-5472; 1538-7445
• DOI: 10.1158/1538-7445.AM2017-236

Abstract Preclinical and epidemiologic data suggest that a unique feature of lipogenesis in cancer cells which has received limited attention is the accumulation of monounsaturated fatty acids (MUFA) which are largely derived from saturated fatty acids (SFA) by the action of stearoyl-Co-A desaturase (SCD-1). Activation of SCD-1, a delta-9 fatty acid desaturase, is considered to be an important factor in the development of obesity and several types of cancer including breast cancer. However, no data are available on how changes in SCD-1 activity induced by potential chemopreventive agents relate to established biomarkers of breast cancer risk. To address this issue, we measured the activity of SCD-1, expressed as the ratios of palmitoleic acid (C16:ln7) to palmitic acid (C16:0) (SCD-16) and oleic acid (C18:ln9) to steric acid (C18:0) (SCD-18) in plasma samples of postmenopausal women enrolled in our recently published clinical trial (Sandhu N, et al Cancer Prev Res 9:275, 2016) designed to test the individual and combined effect of the antiestrogen Raloxifene and the omega-3 preparation Lovaza on breast density, a validated biomarker of breast cancer risk. We observed that daily administration of Lovaza (1,860 mg eicosapentaenoic [EPA] + 1,500 mg docosahexaenoic [DHA]) significantly reduced SCD-1 activity, an effect which was sustained for the two-year duration of the trial. Raloxifene, on the other hand, did not significantly alter SCD-1 activity in our subjects. SCD-1 activity was positively correlated with BMI (for SCD-16, r=0.45, p<01; for SCD-18, r=0.23, p<0.01) and paralleled changes in BMI in the same direction over the two years of the study. These findings support the role of this enzyme in the development of obesity. Importantly, decreasing levels of SCD-1 were found to be associated with a progressive reduction in breast density in obese women (BMI≥30) (for SCD-16; r=0.47, p<0.01; for SCD-18; r=0.36, p<0.05). No correlation between breast density and SCD-1 was observed in non-obese subjects (r=0.02 for SCD-16 and 0.04 for SCD-18). Our results suggest that BMI-related factors play an important role in the reduction of breast density by omega-3 fatty acids. They also indicate that SCD-1 may be a useful biomarker in future clinical trials testing the benefit of nutritional interventions in reducing obesity associated breast cancer risk. Citation Format: Andrea Manni, John P. Richie, Susann E. Schetter, Ana Calcagnotto, Neil Trushin, Cesar Aliaga, Karam El-Bayoumy. Stearoyl-CoA desaturase-1, a novel target of omega-3 fatty acids for reducing breast cancer risk in obese postmenopausal women [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 236. doi:10.1158/1538-7445.AM2017-236