Browse
Submit Data
Databases
API
Help

Dataset Information

25 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Inhibition of CDK2/CyclinE1 by xanthones from the mangosteen (Garcinia mangostana): a structure-activity relationship study.

ABSTRACT: Uncontrolled regulation of cyclin dependent kinases (CDKs) has negative implications in many cancers and malignancies and has recently led to the approval of select CDK inhibitors. Herein we present data reporting that xanthones, a class of compounds isolated from the purple mangosteen (Garcinia mangostana) fruit, can inhibit CDK2/CyclinE1. We evaluated nine different xanthones, including α-mangostin, β-mangostin, γ-mangostin, gartanin, 8-desoxygartanin, garcinone C, garcinone D, 9-hydroxycalabaxanthone, and 3-isomangostin for toxicity in 22Rν1 (prostate cancer cells) and MDA-MB-231 (breast cancer cells). All compounds dose-dependently inhibited the viability of both cell lines. A cell free biochemical assay was performed to determine if selected phytochemicals inhibited CDK2/CyclinE1. γ-Mangostin and α-mangostin were the strongest inhibitors, respectively. The results suggest that the position of key functional groups including hydroxyl and isoprenyl groups contribute to the CDK2 inhibitory effect. Taken together, the evidence suggests that xanthones can directly target CDK2 providing a possible explanation for their therapeutic potential.

SUBMITTER: Nauman MC

PROVIDER: S-EPMC7854934 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Similar Datasets

Xanthones from the Pericarp of Garcinia mangostana.

Project description:Mangosteen (Garcinia mangostana L.) is one of the most popular tropical fruits (called the "Queen of Fruits"), and is a rich source of oxygenated and prenylated xanthone derivatives. In the present work, phytochemical investigation has resulted in one new prenylated xanthone and 13 known xanthones isolated from the pericarp of G. mangostana. Their structures were established by spectroscopic data analysis, including X-ray diffraction. The new one was further tested for cytotoxic activity against seven cancer cell lines (CNE-1, CNE-2, A549, H490, PC-3, SGC-7901, U87), displaying the half maximal inhibitory concentration (IC₅0) values 3.35, 4.01, 4.84, 7.84, 6.21, 8.09, and 6.39 μM, respectively. It is noteworthy that the new compound can promote CNE-2 cells apoptosis in late stage, having a remarkable inhibition effect on the side population growth of CNE-2 at 1.26 μM. The bioactive compound was also detected in extract from fresh mangosteen flesh, which indicated that the popular fruit could have potential cytotoxic activity for cancer cell lines.

| S-EPMC6154529 | biostudies-literature

Cytotoxic prenylated xanthones from the pericarps of Garcinia mangostana.

Project description:Bioassay-guided fractionation of an ethanol extract of the pericarps of Garcinia mangostana led to the isolation of two new prenylated xanthones, named 1,3,7-trihydroxy-2-(3-methyl-2-butenyl)-8-(3-hydroxy-3-methylbutyl)-xanthone (1) and 1,3,8-trihydroxy-2-(3-methyl-2-butenyl)-4-(3-hydroxy-3-methylbutanoyl)-xanthone (2), together with the five known compounds garcinones C (3) and D (4), gartanin (5), xanthone I (6), and γ-mangostin (7). Their structures were elucidated primarily based on MS and NMR data. Compounds 1-7 showed significant cytotoxic activities against various human cancer cell lines.

| S-EPMC6271135 | biostudies-literature

De novo transcriptome assembly of mangosteen (Garcinia mangostana L.) fruit.

Project description:Garcinia mangostana L. (Mangosteen), of the family Clusiaceae, is one of the economically important tropical fruits in Indonesia. In the present study, we performed de novo transcriptomic analysis of Garcinia mangostana L. through RNA-Seq technology. We obtained the raw data from 12 libraries through Ion Proton System. Clean reads of 191,735,809 were obtained from 307,634,890 raw reads. The raw data obtained in this study can be accessible in DDBJ database with accession number of DRA005014 with bioproject accession number of PRJDB5091. We obtained 268,851 transcripts as well as 155,850 unigenes, having N50 value of 555 and 433 bp, respectively. Transcript/unigene length ranged from 201 to 5916 bp. The unigenes were annotated with two main databases from NCBI and UniProtKB, respectively having annotated-sequences of 73,287 and 73,107, respectively. These transcriptomic data will be beneficial for studying transcriptome of Garcinia mangostana L.

| S-EPMC5024146 | biostudies-literature

Prenylated xanthones from mangosteen (Garcinia mangostana) activate the AhR and Nrf2 pathways and protect intestinal barrier integrity in HT-29 cells.

Project description:Xanthones from the tropical fruit mangosteen (Garcinia mangostana) display anti-inflammatory and anti-oxidative activities. Here, we isolate and identify potential inducers of the aryl hydrocarbon receptor (AhR) and nuclear factor erythroid 2-related factor 2 (Nrf2) signaling pathways from mangosteen using a bioassay-guided strategy. Mangosteen fruit pericarp extracts were subjected to sequential solvent extractions, followed by chromatography coupled with NMR spectroscopy and mass spectrometric analyses for identification and isolation of pure compounds. Isolation of active fractions led to seven prenylated xanthones that were identified and subsequently evaluated for bioactivity. In vitro luciferase reporter cellular assays using H1L6.1c3 (AhR induction) and HepG2-ARE (Nrf2 induction) were used to identify AhR and Nrf2 activators. All seven prenylated xanthones displayed AhR inducing activity, whereas only five xanthones activated Nrf2. Garcinone D (GarD) significantly upregulated AhR/Cyp1a1 and Nrf2/HO-1 protein expression and enhanced zonula occludens-1 and occludin protein levels in HT-29 cells. In addition, GarD inhibited oxidative stress-induced intestinal epithelial barrier dysfunction by enhancing tight junction (TJ) proteins and inhibition of reactive oxygen species production. Inhibition of AhR by pretreating cells with an AhR antagonist revealed that the AhR pathway is required for the improved epithelial barrier functions of GarD. These results highlight a dual mechanism by GarD that confers protection against intestinal epithelial barrier dysfunction.

| S-EPMC8647718 | biostudies-literature

Cytotoxic xanthone constituents of the stem bark of Garcinia mangostana (mangosteen).

Project description:Bioassay-guided fractionation of a chloroform-soluble extract of Garcinia mangostana stem bark, using the HT-29 human colon cancer cell line and an enzyme-based ELISA NF-kappaB assay, led to the isolation of a new xanthone, 11-hydroxy-3-O-methyl-1-isomangostin (1). The structure of 1 was elucidated by spectroscopic data analysis. In addition, 10 other known compounds, 11-hydroxy-1-isomangostin (2), 11alpha-mangostanin (3), 3-isomangostin (4), alpha-mangostin (5), beta-mangostin (6), garcinone D (7), 9-hydroxycalabaxanthone (8), 8-deoxygartanin (9), gartanin (10), and cratoxyxanthone (11), were isolated. Compounds 4-8 exhibited cytotoxicity against the HT-29 cell line with ED50 values of 4.9, 1.7, 1.7, 2.3, and 9.1 microM, respectively. In an ELISA NF-kappaB assay, compounds 5-7, 9, and 10 inhibited p65 activation with IC50 values of 15.9, 12.1, 3.2, 11.3, and 19.0 microM, respectively, and 6 showed p50 inhibitory activity with an IC50 value of 7.5 microM. Alpha-mangostin (5) was further tested in an in vivo hollow fiber assay, using HT-29, LNCaP, and MCF-7 cells, but it was found to be inactive at the highest dose tested (20 mg/kg).

| S-EPMC2887388 | biostudies-literature

RNA-seq analysis of mangosteen (<i>Garcinia mangostana</i> L.) fruit ripening.

Project description:Mangosteen (Garcinia mangostana L.) is known for its delectable taste and contains high amount of xanthones which have been reported to possess anti-cancer, anti-inflammatory and other bioactive properties. However, stage-specific regulation of mangosteen fruit ripening has never been studied in detail. We have performed a comparative transcriptomic analysis of three ripening stages (Stage 0, 2 and 6) of mangosteen. We have obtained a raw data from six libraries through Illumina HiSeq 4000. A total of ~ 40 Gb of raw data were generated. Clean reads of 650,887,650 (bp) were obtained from 656,913,570 (bp) raw reads. The raw transcriptome data were deposited to SRA database, with the BioProject accession number of PRJNA339916. These data will be beneficial for transcriptome profiling in order to study the regulation of mangosteen fruit ripening. The lack of a complete sequence database from this species impedes protein identification. These data sets provide a reference data for the exploration of novel genes or proteins to understand mangosteen fruit ripening behaviour.

| S-EPMC5435573 | biostudies-literature

Non-Destructive Chemical Analysis of a Garcinia mangostana L. (Mangosteen) Herbarium Voucher Specimen.

Project description:Herbarium voucher specimens are used primarily for taxonomic confirmation. However, they also afford a record of the metabolic profile of a plant, potentially at the time it was collected, or at the very least, at the time of analysis. Even with the enhanced sensitivity of modern analytical techniques, analysis of the metabolites of a herbarium voucher requires removal and consumption of at least part of an entire specimen. We present herein a non-destructive method to analyze the metabolites of herbarium voucher specimens with the droplet-liquid microjunction-surface sampling probe (droplet probe) coupled to ultra-performance liquid chromatography and highresolution mass spectrometry. As proof of concept, a herbarium voucher specimen of Garcinia mangostana (mangosteen) was utilized due to the well-characterized xanthones biosynthesized by this plant, which are of interest as potential anticancer agents. Also, the juice of the fruits of this plant is used widely in the United States and in other countries as a botanical dietary supplement. Metabolite profiles of the sampled surfaces were compared to a subset of xanthone standards. Using this innovative method on the herbarium voucher specimen, we were able to readily identify cytotoxic prenylated xanthones while maintaining the integrity of the entire specimen.

| S-EPMC6317376 | biostudies-literature

Anti-Bacterial and Anti-Fungal Activity of Xanthones Obtained via Semi-Synthetic Modification of α-Mangostin from Garcinia mangostana.

Project description:The microbial contamination in food packaging has been a major concern that has paved the way to search for novel, natural anti-microbial agents, such as modified α-mangostin. In the present study, twelve synthetic analogs were obtained through semi-synthetic modification of α-mangostin by Ritter reaction, reduction by palladium-carbon (Pd-C), alkylation, and acetylation. The evaluation of the anti-microbial potential of the synthetic analogs showed higher bactericidal activity than the parent molecule. The anti-microbial studies proved that I E showed high anti-bacterial activity whereas I I showed the highest anti-fungal activity. Due to their microbicidal potential, modified α-mangostin derivatives could be utilized as active anti-microbial agents in materials for the biomedical and food industry.

| S-EPMC6155947 | biostudies-literature

Rind from Purple Mangosteen (Garcinia mangostana) Attenuates Diet-Induced Physiological and Metabolic Changes in Obese Rats.

Project description:The pulp of the purple mangosteen, Garcinia mangostana, is a popular tropical fruit but the rind containing xanthones such as α-mangostin together with procyanidins and anthocyanidins is usually discarded as waste. However, this rind has been used in South-East Asia for diarrhoea, dysentery, skin infections and wounds. As xanthones have reported anti-inflammatory and antioxidant responses, this study has determined the bioactive compounds and evaluated the effects of G. mangostana rind on physiological, metabolic, liver and cardiovascular parameters in rats with diet-induced metabolic syndrome. Rats fed a diet with increased simple sugars and saturated fats developed obesity, hypertension, increased left ventricular stiffness, dyslipidaemia and fatty liver. Administration of G. mangostana rind as 5% of the food to rats with diet-induced metabolic syndrome gave a dose of 168 mg/kg/day α-mangostin, 355 mg/kg/day procyanidins, 3.9 mg/kg/day anthocyanins and 11.8 mg/kg/day hydroxycitric acid for 8 weeks which reduced body weight and attenuated physiological and metabolic changes in rats including decreased abdominal fat deposition, decreased abdominal circumference and whole-body fat mass, improved liver structure and function and improved cardiovascular parameters such as systolic blood pressure, left ventricular stiffness and endothelial function. These responses were associated with decreased infiltration of inflammatory cells, decreased deposition of collagen in both heart and liver and decreased mean adipocyte size in retroperitoneal adipose tissues. We conclude that, in rats with diet-induced metabolic syndrome, chronic intake of G. mangostana rind decreased infiltration of inflammatory cells which decreased physiological, metabolic, liver and cardiovascular symptoms.

| S-EPMC7912346 | biostudies-literature

Multitarget Action of Xanthones from <i>Garcinia mangostana</i> against α-Amylase, α-Glucosidase and Pancreatic Lipase.

Project description:Digestive enzymes such α-amylase (AA), α-glucosidase (AG) and pancreatic lipase (PL), play an important role in the metabolism of carbohydrates and lipids, being attractive therapeutic targets for the treatment of type 2 diabetes and obesity. Garcinia mangostana is an interesting species because there have been identified xanthones with the potential to inhibit these enzymes. In this study, the multitarget inhibitory potential of xanthones from G. mangostana against AA, AG and PL was assessed. The methodology included the isolation and identification of bioactive xanthones, the synthesis of some derivatives and a molecular docking study. The chemical study allowed the isolation of five xanthones (1-5). Six derivatives (6-11) were synthesized from the major compound, highlighting the proposal of a new solvent-free methodology with microwave irradiation for obtaining aromatic compounds with tetrahydropyran cycle. Compounds with multitarget activity correspond to 2, 4, 5, 6 and 9, highlighting 6 with IC50 values of 33.3 µM on AA, 69.2 µM on AG and 164.4 µM on PL. Enzymatic kinetics and molecular docking studies showed that the bioactive xanthones are mainly competitive inhibitors on AA, mixed inhibitors on AG and non-competitive inhibitors on PL. The molecular coupling study established that the presence of methoxy, hydroxyl and carbonyl groups are important in the activity and interaction of polyfunctional xanthones, highlighting their importance depending on the mode of inhibition.

| S-EPMC9144329 | biostudies-literature

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data