Garcinol—A Natural Histone Acetyltransferase Inhibitor and New Anti-Cancer Epigenetic Drug

Kopytko, Patrycja; Piotrowska, Katarzyna; Janisiak, Joanna; Tarnowski, Maciej

doi:10.3390/ijms22062828

Cited by 38 publications

(18 citation statements)

References 67 publications

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“…We demonstrate by ChIP that FOXC2 binds to its promoter and its binding affinity is enhanced by LPS treatment. Our data also reveal that garcinol, a HAT inhibitor, that is specific to p300 and PCAF (Balasubramanyam et al, 2004;Kim et al, 2020;Wang et al, 2020;Kopytko et al, 2021), represses LPS-stimulated histone acetylation at FOXC2 promoter, FOXC2 binding affinity and FOXC2 expression in HPMEC-Im. Our data shows that LPS-stimulated FOXC2 expression in primary HPMEC is also repressed by garcinol consistent with our data in immortalized HPMEC.…”

Section: Discussionsupporting

confidence: 60%

FOXC2 Autoregulates Its Expression in the Pulmonary Endothelium After Endotoxin Stimulation in a Histone Acetylation-Dependent Manner

Sheng

Menden

et al. 2021

Front. Cell Dev. Biol.

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The innate immune response of pulmonary endothelial cells (EC) to lipopolysaccharide (LPS) induces Forkhead box protein C2 (FOXC2) activation through Toll Like Receptor 4 (TLR4). The mechanisms by which FOXC2 expression is regulated in lung EC under LPS stimulation remain unclear. We postulated that FOXC2 regulates its own expression in sepsis, and its transcriptional autoregulation directs lymphatic EC cell-fate decision. Bioinformatic analysis identified potential FOXC2 binding sites in the FOXC2 promoter. In human lung EC, we verified using chromatin immunoprecipitation (ChIP) and luciferase assays that FOXC2 bound to its own promoter and stimulated its expression after LPS stimulation. Chemical inhibition of histone acetylation by garcinol repressed LPS-induced histone acetylation in the FOXC2 promoter region, and disrupted LPS-mediated FOXC2 binding and transcriptional activation. CRISPR/dCas9/gRNA directed against FOXC2-binding-element (FBE) suppressed LPS-stimulated FOXC2 binding and autoregulation by blocking FBEs in the FOXC2 promoter, and repressed expression of lymphatic EC markers. In a neonatal mouse model of sterile sepsis, LPS-induced FOXC2 binding to FBE and FOXC2 expression in lung EC was attenuated with garcinol treatment. These data reveal a new mechanism of LPS-induced histone acetylation-dependent FOXC2 autoregulation.

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Section: Discussionsupporting

confidence: 60%

FOXC2 Autoregulates Its Expression in the Pulmonary Endothelium After Endotoxin Stimulation in a Histone Acetylation-Dependent Manner

Sheng

Menden

et al. 2021

Front. Cell Dev. Biol.

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“…[ 28–30 ] These promising in vivo results warrant further investigation of garcinol as a potential antiviral drug candidate although in vitro assays with tumor cell lines revealed considerable cytotoxicity for it and its manifold antitumor activities are indeed well described. [ 28,30,36,37 ] Furthermore, a chemical fine‐tuning of garcinol might improve its affinity for HIV‐1 RT‐associated RNase H and related viral ribonucleases with Mg 2+ ‐dependent active sites. For instance, the exonuclease activity of coronavirus Nsp14 protein depends on Mg 2+ and can be a highly relevant target for such metal‐chelating compounds in future studies.…”

Section: Discussionmentioning

confidence: 99%

Garcinol from Garcinia indica inhibits HIV‐1 reverse transcriptase‐associated ribonuclease H

Corona

Seibt

Schaller

et al. 2021

Archiv der Pharmazie

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The bioactive components of Garcinia indica, garcinol (camboginol), and isogarcinol (cambogin), are suitable drug candidates for the treatment of various human diseases. HIV‐1‐RNase H assay was used to study the RNase H inhibition by garcinol and isogarcinol. Docking of garcinol into the active site of the enzyme was carried out to rationalize the difference in activities between the two compounds. Garcinol showed higher HIV‐1‐RNase H inhibition than the known inhibitor RDS1759 and retained full potency against the RNase H of a drug‐resistant HIV‐1 reverse transcriptase form. Isogarcinol was distinctly less active than garcinol, indicating the importance of the enolizable β‐diketone moiety of garcinol for anti‐RNase H activity. Docking calculations confirmed these findings and suggested this moiety to be involved in the chelation of metal ions of the active site. On the basis of its HIV‐1 reverse transcriptase‐associated RNase H inhibitory activity, garcinol is worth being further explored concerning its potential as a cost‐effective treatment for HIV patients.

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“…Also, garcinol was reported to have antioxidant effects through high free-radical, superoxide anion (O 2-) scavenging activity [21,22], and to have neuroprotective properties by functioning as a histone acetyltransferase inhibitor (HAT) [23]. In addition, recent studies demonstrated its anticancer effects by inducing apoptosis and cell cycle arrest, inhibiting of angiogenesis, and regulating of gene expression in oncogenic cells [24]. Garcinia indica is a plant native to certain regions of India [25].…”

Section: Introductionmentioning

confidence: 99%

Pharmacological Activity of Garcinia indica (Kokum): An Updated Review

Lim

Lee

et al. 2021

Pharmaceuticals

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Garcinia indica (commonly known as kokum), belonging to the Clusiaceae family (mangosteen family), is a tropical evergreen tree distributed in certain regions of India. It has been used in culinary and industrial applications for a variety of purposes, including acidulant in curries, pickles, health drinks, wine, and butter. In particular, G. indica has been used in traditional medicine to treat inflammation, dermatitis, and diarrhea, and to promote digestion. According to several studies, various phytochemicals such as garcinol, hydroxycitric acid (HCA), cyanidin-3-sambubioside, and cyanidin-3-glucoside were isolated from G. indica, and their pharmacological activities were published. This review highlights recent updates on the various pharmacological activities of G. indica. These studies reported that G. indica has antioxidant, anti-obesity, anti-arthritic, anti-inflammatory, antibacterial, hepatoprotective, cardioprotective, antidepressant and anxiolytic effects both in vitro and in vivo. These findings, together with previously published reports of pharmacological activity of various components isolated from G. indica, suggest its potential as a promising therapeutic agent to prevent various diseases.

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Garcinol—A Natural Histone Acetyltransferase Inhibitor and New Anti-Cancer Epigenetic Drug

Cited by 38 publications

References 67 publications

FOXC2 Autoregulates Its Expression in the Pulmonary Endothelium After Endotoxin Stimulation in a Histone Acetylation-Dependent Manner

FOXC2 Autoregulates Its Expression in the Pulmonary Endothelium After Endotoxin Stimulation in a Histone Acetylation-Dependent Manner

Garcinol from Garcinia indica inhibits HIV‐1 reverse transcriptase‐associated ribonuclease H

Pharmacological Activity of Garcinia indica (Kokum): An Updated Review

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