Journal
ONCOTARGET
Volume 7, Issue 39, Pages 63679-63689Publisher
IMPACT JOURNALS LLC
DOI: 10.18632/oncotarget.11626
Keywords
leucine deprivation; breast cancer; proliferation; apoptosis
Categories
Funding
- National Natural Science Foundation [81130076, 81325005, 31271269, 81100615, 81390350, 81300659, 81570777]
- Chinese Academy of Sciences
- Youth Innovation Promotion Association CAS
- SA-SIBS scholarship program
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Substantial studies on fatty acid synthase (FASN) have focused on its role in regulating lipid metabolism and researchers have a great interest in treating cancer with dietary manipulation of amino acids. In the current study, we found that leucine deprivation caused the FASN-dependent anticancer effect. Here we showed that leucine deprivation inhibited cell proliferation and induced apoptosis of MDA-MB-231 and MCF-7 breast cancer cells. In an in vivo tumor xenograft model, the leucine-free diet suppressed the growth of human breast cancer tumors and triggered widespread apoptosis of the cancer cells. Further study indicated that leucine deprivation decreased expression of lipogenic gene FASN in vitro and in vivo. Over-expression of FASN or supplementation of palmitic acid (the product of FASN action) blocked the effects of leucine deprivation on cell proliferation and apoptosis in vitro and in vivo. Moreover, leucine deprivation suppressed the FASN expression via regulating general control non-derepressible (GCN) 2 and sterol regulatory element-binding protein 1C (SREBP1C). Taken together, our study represents proof of principle that anticancer effects can be obtained with strategies to deprive tumors of leucine via suppressing FASN expression, which provides important insights in prevention of breast cancer via metabolic intervention.
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