Inhibition of Fatty Acid Synthase by Polyphenols

Tian, Wei-Xi

doi:10.2174/092986706776361012

Cited by 109 publications

(68 citation statements)

References 30 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Although the detailed mechanism of the inhibitory effect of polyphenols on FASN was not fully understood, the structure activity association analysis demonstrated that the flavonoids containing two hydroxyl groups in the B ring and 5, 7-hydroxyl groups in the A ring with C-2, 3 double bond were the most potent inhibitors on FASN (31). Patuletin (3,5,7,3',4'-pentahydroxy-6-methoxy-flavone) (Fig.…”

Section: Introductionmentioning

confidence: 99%

Patuletin induces apoptosis of human breast cancer SK‑BR‑3 cell line via inhibiting fatty acid synthase gene expression and activity

Zhu

Wang

et al. 2017

Oncol Lett

View full text Add to dashboard Cite

Abstract. Fatty acid synthase (FASN) is a key enzyme involved in fatty acid biosynthesis and serves an important role in breast cancer development. The aim of the present study was to investigate the effects of patuletin on the gene expression and activity of FASN in the human breast cancer SK-BR-3 cell line, and the apoptotic effects of patuletin to breast cancer cells. Quantitative reverse transcription polymerase chain reaction, western blotting and intracellular FASN activity assays were used to evaluate FASN gene expression, protein expression and activity in patuletin-treated SK-BR-3 cells. MTT assays and flow cytometry were used to measure cell growth and cell apoptosis, respectively, following patuletin treatment. As a result, it was demonstrated that patuletin dose-dependently reduces FASN expression and intracellular activity in human breast cancer cells, and induces apoptosis in FASN over-expressing SK-BR-3 cells. Notably, apoptosis is associated with the reduction of intracellular FASN activity. The present study demonstrates that patuletin may be considered as a novel natural inhibitor of FASN, may induce anti-proliferative and pro-apoptotic effects in certain human breast cancer cells and may be useful for preventing and/or treating human breast cancer. IntroductionFatty acid synthase (FASN) is a multi-enzyme that catalyzes the de novo synthesis of palmitate (C16:0, a long-chain saturated fatty acid) from acetyl-CoA and malonyl-CoA, in the presence of NADPH (1). FASN is not only a key factor in the role of fatty acid biosynthesis for energy storage (2,3), but also its expression level increases significantly in adipose tissues and a variety of human carcinomas, including liver, breast, prostate, lung, endometrium, ovary, colon and pancreatic cancer (4-13). This prominent difference of FASN expression between normal and neoplastic tissues makes FASN a potential diagnostic tumor marker (14).Breast cancer is the most common type of cancer and a leading cause of cancer-associated mortalities among females, with a common feature of abnormal cell apoptosis in its development (15). In addition, high levels of FASN expression has been demonstrated to be associated with poor clinical outcome in breast carcinomas, suggesting that FASN expression and tumor aggressiveness are closely associated (4,16). It was identified that obesity may serve a crucial role in the incidence and progression of breast cancer (17). According to the close association between FASN, obesity and breast cancer, the studies of FASN inhibitors have indicated their role as targets for chemotherapy in breast cancer and a novel strategy for antineoplastic intervention (18). In fact, previous studies demonstrated that certain synthetic and natural FASN inhibitors, including C75, desoxyrhaponticin, rhaponticin and α-mangostin may lead to selective cytotoxicity in FASN over-expressing cancer cell lines (18)(19)(20). This result suggested again that the pharmacological inhibition of FASN may represent a potential target for drug development.In...

show abstract

Section: Introductionmentioning

confidence: 99%

Patuletin induces apoptosis of human breast cancer SK‑BR‑3 cell line via inhibiting fatty acid synthase gene expression and activity

Zhu

Wang

et al. 2017

Oncol Lett

View full text Add to dashboard Cite

show abstract

“…However, the most polar solvent ethanol extracted the least inhibitors. It is shown that the FAS inhibitors in Alliums were different from the known natural FAS inhibitors, such as tea-polyphenols and flavonoids (Tian, 2006).In this study, the results showed that the extracts of Alliums strongly inhibited FAS and the mechanism might be related to the interaction with essential sulphydryl groups of FAS. In addition, different inhibitors could exist in various Allium plants.…”

mentioning

confidence: 61%

Section: Resultsmentioning

confidence: 91%

Inhibitory Effects of Allium Vegetable Extracts on Fatty Acid Synthase

Sun

Tian

2009

FSTR

Self Cite

View full text Add to dashboard Cite

Allium vegetables have been shown to have beneficial effects against several diseases, including hyperlipidemia and cancer. This study was carried out with enzymatic method to investigate the inhibition on fatty acid synthase by nine Allium vegetables to explore their health protective mechanisms. It was found the fatty acid synthase inhibitors in most Allium vegetables extracts were concentrated in the lower polar solvents and the inhibition could be reversed by dithiothreitol. Ethyl acetate extract of red onion (Allium cepa L., IC 50 = 0.45 μg/mL) was the most active of the samples tested. In garlic, diallyl trisulfide was suggested to be an effective component which may react with the essential sulphydryl groups in the enzyme. Additionally, the Chinese chive (Allium tuberosum L.) exhibited the most total inhibitory capacity, and its inhibitory components showed more polar than that of other Allium vegetables. It is suggested that different inhibitors of FAS exist in these vegetables.Keywords: fatty acid synthase, Allium, sulfides, enzyme inhibition *To whom correspondence should be addressed. E-mail: tianweixi@gucas.ac.cn IntroductionThe animal fatty acid synthase (EC 2.3.1.85, FAS) is an important enzyme in energy metabolism in vivo. It catalyzes the de novo synthesis of long chain fatty acid from acetylCoA and malonyl-CoA in the presence of NADPH (Smith, 1994). FAS function is related to many human diseases such as cancer and obesity. Human cancer cells express high levels of FAS. The inhibitors of FAS such as cerulenin, C75 and EGCG were reported to be selectively cytotoxic to human cancer cells including breast, ovary, colon, leukemia, prostate and pancreatic tumors, and they exhibited growth inhibition on some human cancers such as ovarian cancer and prostate tumor (Kuhajda, 2006;Kuhajda et al., 2000;Lyn-Cook et al.,1999). The fatty-acid synthesis as a target pathway for chemotherapy development has been identified by these studies with FAS inhibitors (Kuhajda, 2006). In addition, mice treated with cerulenin or C75 exhibited dramatic decreases in food intake and body weight. This action appears to be mediated by malonyl-coA that is main substrate of FAS (Loftus et al., 2000). Therefore, FAS is drawing more and more attention world-wide for its association with human diseases and it might be a possible therapeutic target for both cancer and obesity. The weight-control and anti-cancer functions of teas and tea-polyphenols incarnate the double target character of FAS. The extracts of green tea and black tea, and their components gallated catechins and theaflavin had been reported to be effective inhibitors of FAS (Du et al., 2005;Wang and Tian, 2001;Zhang et al., 2006).Besides the well known garlic (Allium sativum L.) and onion (Allium cepa L.), several other Allium species are widely grown for culinary use, such as scallion (Allium fistulosum L.), chive (Allium schoenoprasum L.) and Chinese chive (Allium tuberosum L.). Since ancient times, these Allium vegetables have been used as common foods and for the ...

show abstract

“…Epigallocatechin gallate (EGCG) and epicatechin gallate (ECG) inhibit FAS with IC50 values of 52 microM and 42 microM mainly by reacting on the beta-ketoacyl reductase (KR) domain of FAS. The inhibitory ability of catechin gallate (CG) is 15 and 12 folds higher than that of EGCG and ECG (39,40). Nowadays, great progress has been made in the study of fatty acid synthase inhibitor from traditional Chinese medicine.…”

Section: Fatty Acid Synthetase Inhibitormentioning

confidence: 99%

Anti-obesity effect of traditional Chinese medicine and natural products

Chen¹,

Lian²,

Lyu³

et al. 2016

Eur J Bio Med Res

View full text Add to dashboard Cite

Abstract:As obesity has become a worldwide health problem over the past three decades, more emphasis are placed on the prevention and treatment of obesity.Research in the nutrition field has recently aroused considerable interest based on the potential of traditional Chinese medicine and natural products to counteract obesity. This review focuses on the anti-obesity action usingtraditional Chinese medicine and natural products. Some present potent anti-obesity effects because of their ability to reduce blood lipid or blood glucose while others could be used for the treatment of obesity as lipase inhibitor, lipid metabolism regulators, appetite suppressants or fatty acid synthase inhibitor. Further study should be conducted in the mechanisms and active ingredients of traditional Chinese medicine and natural products.

show abstract

Inhibition of Fatty Acid Synthase by Polyphenols

Cited by 109 publications

References 30 publications

Patuletin induces apoptosis of human breast cancer SK‑BR‑3 cell line via inhibiting fatty acid synthase gene expression and activity

Patuletin induces apoptosis of human breast cancer SK‑BR‑3 cell line via inhibiting fatty acid synthase gene expression and activity

Inhibitory Effects of Allium Vegetable Extracts on Fatty Acid Synthase

Anti-obesity effect of traditional Chinese medicine and natural products

Contact Info

Product

Resources

About