Inhibition of fatty acid synthase by ginkgolic acids from the leaves of Ginkgo biloba and their cytotoxic activity

Oh, Joonseok; Hwang, In Hyun; Hong, Chul−Un; Lyu, Su-Yun; Na, MinKyun

doi:10.3109/14756366.2012.658786

Cited by 32 publications

(22 citation statements)

References 19 publications

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“…Various mechanisms have been reported, regarding the cytotoxic and anticancer activities of GA. They activate protein phosphatase 2C (PP2C) [4] and inhibit fatty acid synthase (FAS) [29], and α-glucosidase [30]. In addition, GA inhibited de novo lipogenesis in cancer cells by activating AMPK signaling and lowering the expression of enzymes involved in lipogenesis, including acetyl-CoA carboxylase (ACC), fatty acid synthase (FASN) [14].…”

Section: Discussionmentioning

confidence: 99%

Ginkgolic acids inhibit migration in breast cancer cells by inhibition of NEMO sumoylation and NF-κB activity

Hamdoun

Efferth

2017

Oncotarget

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Ginkgolic acids (GA), a group of alkyl phenols found in crude extracts of Ginkgo biloba leaves, are known to have anticancer activity, but their mode of action is not well understood. Our aim in this study was to investigate the anti-migratory activity of seven GA against breast cancer cells and to determine the molecular mechanism behind this activity. All seven GA and their mixture inhibited wound healing in MCF-7 and MDA-MB 231 breast cancer cells. None of the compounds nor the mixture showed cytotoxicity towards the two cell lines, if tested by the resazurin assay. C13:0 inhibited NF-κB activity in the HEK Blue Null 1 reporter cell line. Furthermore, C13:0 inhibited degradation of nuclear factor of κ-light polypeptide gene enhancer in B-cells inhibitor α (IκBα). Sumoylation assay revealed that GA inhibited sumoylation of NF-κB essential modulator (NEMO). Molecular docking on SUMO-activating enzyme E1 showed that the seven GA bound to the active adenylation site with high calculated affinities ranging from -10.28 to -12.27 kcal/mol. Quantitative RT-PCR using C15:0, C13:0 and the mixture showed a significant down-regulation of urokinase plasminogen activator (uPA), plasminogen activator inhibitor-1 (PAI-1), C-X-C chemokine receptor type 4 (CXCR4) and matrix metalloproteinase 9 (MMP-9). We conclude that GA revealed considerable anti-migratory activity at non-cytotoxic concentrations, indicating anti-metastatic activity with low toxicity. This effect can be explained by the inhibition of NEMO sumoylation leading to inhibition of IκBα degradation and consequently a reduction of NF-κB activity, leading to the down-regulation of metastasis related genes including uPA, PAI-1, CXCR4, and MMP-9.

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Section: Discussionmentioning

confidence: 99%

Ginkgolic acids inhibit migration in breast cancer cells by inhibition of NEMO sumoylation and NF-κB activity

Hamdoun

Efferth

2017

Oncotarget

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“…(−)‐Epigallocatechin gallate (EGCG) is a polyphenol found in tea with demonstrated potency against the KR domain of FASN, and is perhaps the most noteworthy of the natural flavonols reported with FASN inhibitory activity (Wang et al, ). More recently, ginkgolic acids (Oh et al, ) and a variety of natural products from Chinese medicine (Cheng et al, ) and spices (Jiang et al, ) have been shown to inhibit FASN. Additional natural product FASN inhibitors with cytotoxic effects on BC cell lines include tannic acid (Nie et al, ), sea buckthorn procyanidins (Wang et al, ), α‐Mangostin (Li et al, ), stilbene glycosides from rhubarb (Li et al, ), and amentoflavone (Lee et al, ).…”

Section: Oncogenic Antigen 519mentioning

confidence: 99%

Fatty Acids and Breast Cancer: Make Them on Site or Have Them Delivered

Kinlaw

Baures

Lupien

et al. 2016

Journal Cellular Physiology

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Brisk fatty acid (FA) production by cancer cells is accommodated by the Warburg effect. Most breast and other cancer cell types are addicted to fatty acids (FA), which they require for membrane phospholipid synthesis, signaling purposes, and energy production. Expression of the enzymes required for FA synthesis is closely linked to each of the major classes of signaling molecules that stimulate BC cell proliferation. This review focuses on the regulation of FA synthesis in BC cells, and the impact of FA, or the lack thereof, on the tumor cell phenotype. Given growing awareness of the impact of dietary fat and obesity on BC biology, we will also examine the less-frequently considered notion that, in addition to de novo FA synthesis, the lipolytic uptake of preformed FA may also be an important mechanism of lipid acquisition. Indeed, it appears that cancer cells may exist at different points along a “lipogenic-lipolytic axis”, and FA uptake could thwart attempts to exploit the strict requirement for FA focused solely on inhibition of de novo FA synthesis. Strategies for clinically targeting FA metabolism will be discussed, and the current status of the medicinal chemistry in this area will be assessed.

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“…The extracts from G. biloba play an important role on many nervous system diseases including Alzheimer's disease, protecting hippocampal neurons, et al . Ginkgolic acids (GAs) are important constituents and possess beneficial effects, including anti‐cancer, anti‐parasitism, anti‐bacterial and molluscicidal activity , particularly the inhibition of enzymes, including HIV protease, fatty acid synthase, et al . GAs are abundant in the sarcotesta of G. biloba over 4%, w/w .…”

Section: Introductionmentioning

confidence: 99%

Application of coordination agent in high‐speed counter‐current chromatography for the preparative separation and isolation ginkgolic acids from the sarcotesta of Ginkgo biloba L

Zhu

Jiang

et al. 2018

J of Separation Science

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An efficient coordination high‐speed counter‐current chromatography method for the preparative separation of ginkgolic acids from the sarcotesta of Ginkgo biloba L was developed. The type, concentration, and mechanism of the coordination agent were investigated. Following the use of four types of metal salts including silver nitrate, copper chloride, ferric chloride, and aluminium nitrate, n‐heptane/ethyl acetate/methanol/acetic acid 5:4:1:1, v/v with 0.20 mol/L silver nitrate as the coordination agent was chosen as the optimum two‐phase solvent system. Five main ginkgolic acids including C13:0, C15:0, C15:1, C17:1, and C17:2 were successfully separated with purities greater than 98%. The sample loading was 500 mg, the flow‐rate was 2.0 mL/min, rotation speed was 800 rpm and temperature was 20°C. The structures of the separated ginkgolic acids were identified by comparison with standard samples and electrospray ionization mass spectrometry. The introduction of coordination chemistry in high‐speed counter‐current chromatography is novel and effective for the preparative separation and isolation of ginkgolic acids from the sarcotesta of Ginkgo biloba L and could also be applied to separate compounds which form coordination bonds in other complex natural products.

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Inhibition of fatty acid synthase by ginkgolic acids from the leaves of Ginkgo biloba and their cytotoxic activity

Cited by 32 publications

References 19 publications

Ginkgolic acids inhibit migration in breast cancer cells by inhibition of NEMO sumoylation and NF-κB activity

Ginkgolic acids inhibit migration in breast cancer cells by inhibition of NEMO sumoylation and NF-κB activity

Fatty Acids and Breast Cancer: Make Them on Site or Have Them Delivered

Application of coordination agent in high‐speed counter‐current chromatography for the preparative separation and isolation ginkgolic acids from the sarcotesta of Ginkgo biloba L

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