Liang Yan, Luo Di, Gao Xuan, Wu Hao
School of Kinesiology and Health, Capital University of Physical Education and Sports Beijing 100191 China
Scientific Research Office, Capital University of Physical Education and Sports Beijing 100191 China
RSC Adv. 2018 Feb 20;8(15):8112-8117. doi: 10.1039/c7ra13246h. eCollection 2018 Feb 19.
Fatty acid synthase (FAS) is highly expressed in human adipocytes and cancer cells and is considered as a dual therapeutic target for obesity and cancer treatment. Garcinone E is a natural xanthone and exists in the pericarp of . In previous studies, xanthones were reported to be highly active inhibitors of FAS. In the present study, the detailed inhibitory mechanism of garcinone E on FAS was investigated. We found that garcinone E inhibited the activity of FAS in a concentration-dependent manner with a half-inhibitory concentration value of 3.3 μM. The inhibition kinetic results showed that the inhibition of FAS by garcinone E was competitive with respect to acetyl-CoA, mixed competitive and noncompetitive with respect to malonyl-CoA, and noncompetitive to NADPH. In addition, garcinone E showed irreversible inhibition on FAS, which was different from all other xanthones. Since FAS is believed to be a therapeutic target for obesity and cancer treatment, these findings suggest the clinical potential of garcinone E in the prevention and treatment of both obesity and cancer.
脂肪酸合酶（FAS）在人类脂肪细胞和癌细胞中高表达，被认为是肥胖症和癌症治疗的双重治疗靶点。藤黄酮E是一种天然的氧杂蒽酮，存在于[植物名称]的果皮中。在先前的研究中，氧杂蒽酮被报道为FAS的高效抑制剂。在本研究中，对藤黄酮E抑制FAS的详细机制进行了研究。我们发现藤黄酮E以浓度依赖性方式抑制FAS的活性，半抑制浓度值为3.3μM。抑制动力学结果表明，藤黄酮E对FAS的抑制作用相对于乙酰辅酶A是竞争性的，相对于丙二酰辅酶A是混合竞争性和非竞争性的，对NADPH是非竞争性的。此外，藤黄酮E对FAS表现出不可逆抑制作用，这与所有其他氧杂蒽酮不同。由于FAS被认为是肥胖症和癌症治疗的治疗靶点，这些发现表明藤黄酮E在预防和治疗肥胖症和癌症方面具有临床潜力。
