Fatty acid synthase inhibitors of phenolic constituents isolated from Garcinia mangostana

Jiang, Huifen; Quan, Xiao Fang; Tian, Wei; Hu, Jiang; Wang, Peng Cheng; Huang, Sheng; Cheng, Zhong Quan; Wen, Liang; Zhou, Jun; Feng, Xisheng; Zhao, You Xing

doi:10.1016/j.bmcl.2010.08.061

Cited by 54 publications

(37 citation statements)

References 44 publications

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“…In our previous study, α-mangostin was found to inhibit FAS overall reaction with IC 50 value of 5.54 µM [38]. In this study, we assayed its inhibition kinetics to explore its specific acting sites on FAS.…”

Section: Discussionmentioning

confidence: 98%

α-Mangostin Induces Apoptosis and Suppresses Differentiation of 3T3-L1 Cells via Inhibiting Fatty Acid Synthase

Quan

Wang

et al. 2012

PLoS ONE

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α-Mangostin, isolated from the hulls of Garcinia mangostana L., was found to have in vitro cytotoxicity against 3T3-L1 cells as well as inhibiting fatty acid synthase (FAS, EC 2.3.1.85). Our studies showed that the cytotoxicity of α-mangostin with IC50 value of 20 µM was incomplicated in apoptotic events including increase of cell membrane permeability, nuclear chromatin condensation and mitochondrial membrane potential (ΔΨm) loss. This cytotoxicity was accompanied by the reduction of FAS activity in cells and could be rescued by 50 µM or 100 µM exogenous palmitic acids, which suggested that the apoptosis of 3T3-L1 preadipocytes induced by α-mangostin was via inhibition of FAS. Futhermore, α-mangostin could suppress intracellular lipid accumulation in the differentiating adipocytes and stimulated lipolysis in mature adipocytes, which was also related to its inhibition of FAS. In addition, 3T3-L1 preadipocytes were more susceptible to the cytotoxic effect of α-mangostin than mature adipocytes. Further studies showed that α-mangostin inhibited FAS probably by stronger action on the ketoacyl synthase domain and weaker action on the acetyl/malonyl transferase domain. These findings suggested that α-mangostin might be useful for preventing or treating obesity.

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Section: Discussionmentioning

confidence: 98%

α-Mangostin Induces Apoptosis and Suppresses Differentiation of 3T3-L1 Cells via Inhibiting Fatty Acid Synthase

Quan

Wang

et al. 2012

PLoS ONE

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“…*p<0.05 vs. control group; **p<0.01 vs. control group; ***p<0.001 vs. control group Efforts to identify prognostic factors for ovarian cancer are needed, and diet may provide a modifiable influence on survival. Herbal medicines have been proven to be a major source of novel agents with various pharmaceutical activities [31][32][33][34][35]. Natural products have provided a rich source of drugs for many diseases, including cancer.…”

Section: Discussionmentioning

confidence: 99%

Calycosin induces apoptosis in human ovarian cancer SKOV3 cells by activating caspases and Bcl-2 family proteins

2015

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Calycosin is widely used as a natural active compound for its anti-oxidative and anti-inflammation activity. Recently, several studies have shown that calycosin can inhibit growth and induce apoptosis in human cancer cell lines; however, the mechanisms are not completely clarified yet. In this study, we investigated the effects of calycosin on human ovarian carcinoma SKOV3 cells, as well as the mechanisms. SKOV3 cells were treated with calycosin at a series of concentrations for different times. In vitro, the MTT assay showed that calycosin had obvious anti-proliferation effects on SKOV3 cells in a dose- and time-dependent manner. Cell morphological changes which expressed by Hoechst 33258 staining were compared with apoptotic changes detected by fluorescence microscope. Compared with control group, the group treated with calycosin showed a significant increase in apoptosis rate. Expression of apoptosis related Bax/Bcl-2 and caspases proteins were detected by Western blotting. The results demonstrated that calycosin up-regulated the Bax/Bcl-2 ratio and cleaved caspase-3, cleaved caspase-9 expression in a dose-dependent manner. In summary, calycosin might exert anti-growth and induce-apoptosis activity against ovarian cancer SKOV3 cells through activating caspases and Bcl-2 family proteins, therefore presenting as a promising therapeutic agent for the treatment of ovarian cancer.

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“…In previous studies, a number of dietary polyphenols, including α-mangostin, resveratrol, curcumin and quercetin exhibited high inhibitory activity against FASN (21)(22)(23)(24)(25)(26)(27)(28)(29)(30). 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).…”

Section: Introductionmentioning

confidence: 95%

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

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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...

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Fatty acid synthase inhibitors of phenolic constituents isolated from Garcinia mangostana

Cited by 54 publications

References 44 publications

α-Mangostin Induces Apoptosis and Suppresses Differentiation of 3T3-L1 Cells via Inhibiting Fatty Acid Synthase

α-Mangostin Induces Apoptosis and Suppresses Differentiation of 3T3-L1 Cells via Inhibiting Fatty Acid Synthase

Calycosin induces apoptosis in human ovarian cancer SKOV3 cells by activating caspases and Bcl-2 family proteins

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

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