| First Author | Gluschnaider U | Year | 2014 |
| Journal | Cancer Res | Volume | 74 |
| Issue | 23 | Pages | 6991-7002 |
| PubMed ID | 25304261 | Mgi Jnum | J:217171 |
| Mgi Id | MGI:5613275 | Doi | 10.1158/0008-5472.CAN-14-0385 |
| Citation | Gluschnaider U, et al. (2014) Long-chain fatty acid analogues suppress breast tumorigenesis and progression. Cancer Res 74(23):6991-7002 |
| abstractText | Obesity and type 2 diabetes (T2D) are associated with increased breast cancer incidence and mortality, whereas carbohydrate-restricted ketogenic diets ameliorate T2D and suppress breast cancer. These observations suggest an inherent efficacy of nonesterified long-chain fatty acids (LCFA) in suppressing T2D and breast tumorigenesis. In this study, we investigated novel antidiabetic MEDICA analogues consisting of methyl-substituted LCFA that are neither beta-oxidized nor esterified to generate lipids, prompting interest in their potential efficacy as antitumor agents in the context of breast cancer. In the MMTV-PyMT oncomouse model of breast cancer, in which we confirmed that tumor growth could be suppressed by a carbohydrate-restricted ketogenic diet, MEDICA treatment suppressed tumor growth, and lung metastasis, promoting a differentiated phenotype while suppressing mesenchymal markers. In human breast cancer cells, MEDICA treatment attenuated signaling through the STAT3 and c-Src transduction pathways. Mechanistic investigations suggested that MEDICA suppressed c-Src-transforming activity by elevating reactive oxygen species production, resulting in c-Src oxidation and oligomerization. Our findings suggest that MEDICA analogues may offer therapeutic potential in breast cancer and overcome the poor compliance of patients to dietary carbohydrate restriction. |
