Mangosteen Fruit Research Articles

Adipocyte reporter assays: Application for identification of anti‐inflammatory and antioxidant properties of mangosteen xanthones

Three fluorescence biosensors were developed based on a 3T3-L1 preadipocyte line that stably expressed Nfkb-RE/GFP, Fabp4-P/CFP, and Nrf2-P/YFP fluorescent reporters. We hypothesized that nutraceuticals' inflammatory, adipogenic, and antioxidant status will be identified based on the change in fluorescence in reporter adipocytes. We validated these assays with activators of NFκB, FABP4-regulating peroxisome proliferator activated receptor gamma, NFR2 and, thereafter, tested known and unknown properties of mangostines (MGs), the xanthone metabolites in mangosteen fruit. We validated inflammatory and adipogenic properties of α-MG using an Nfkb-RE/GFP biosensor assay. Next, we identified unique properties of γ-MG, a minor MG xanthone. γ-MG suppressed adipogenesis and expression of adiponectin, but inhibited the Nfkb-RE/GFP reporter and secretion of inflammatory monocyte chemotactic protein 1 as compared to the control adipocytes. We found that the inhibition of adipogenesis and Nfkb-mediated inflammation depends on a dose-dependent reduction of Nrf2 promoter activity by α-MG. The Nrf2 inhibition resulted in the reduced Pparg expression. α-MG did not directly influence Pparg activity in Fabp4-P/CFP adipocytes. α-MG-mediated antioxidant response via Nrf2 is a mechanism preventing adipogenesis and inflammation in adipocytes. Combined application of high-throughput biosensors could provide an effective platform for the identification of nutraceuticals and the mechanism of their actions in adipocytes and, potentially, in obese patients.

Optimized extraction and characterization of antimicrobial phenolic compounds from mangosteen (Garcinia mangostana L.) cultivation and processing waste

Applications for antimicrobials derived from the mangosteen (Garcinia mangostana L.) plant are presently restricted by high production costs. Extraction from cultivation or processing waste streams using a solvent-free approach could lessen to permit commercial applications in food processing and preservation. Phenolics were extracted from mangosteen bark, leaf and fruit pericarp in methanol and in water using response surface methodology to optimize recovery. Initial examination of antimicrobial effects revealed a lack of antimicrobial activity against fungi and weak activity against the Gram-negative bacteria Escherichia coli and Salmonella typhimurium. In contrast, extracts prepared from bark or fruit pericarp exhibited strong pH-dependent bacteriostatic and bactericidal effects against Listeria monocytogenes and Staphylococcus aureus. Activity was slightly weaker in aqueous extracts due to lower concentrations of tartaric acid esters and flavonols than in methanolic extracts. Measurement of propidium iodide uptake and ATP leakage indicated that the extracts induced damage to the membrane of Gram-positive bacteria. Extracts of mangosteen bark and fruit pericarp contain mixtures of phenolic compounds with activity against Gram-positive bacteria, notably Listeria monocytogenes. Extraction of phenolics from mangosteen waste could yield fractions for potential applications in the formulation of low-cost processing aids or sanitizers for the food industry.

Inhibitory effects of α-mangostin on mammalian DNA polymerase, topoisomerase, and human cancer cell proliferation

We found that the ethanol extract of mangosteen (Garcinia mangostana L.) fruit rind had a strong inhibitory effect on mammalian DNA polymerase (pol) activity and isolated α-mangostin as a potent pol inhibitor from the extract. In this study, the inhibitory activities against mammalian pols by α-mangostin and its related five compounds, 3-isomangostin, xanthone, 9,10-anthraquinone, 9-anthracenecarboxylic acid, and anthracene, were investigated. α-Mangostin was the most potent inhibitor of the mammalian pol species among the tested compounds, with IC₅₀ values of 14.8-25.6 μM. This compound also inhibited human DNA topoisomerases (topos) I and II activities with IC₅₀ values of 15.0 and 7.5 μM, respectively, but did not inhibit the activities of other DNA metabolic enzymes tested. α-Mangostin also did not directly bind to double-stranded DNA as determined by thermal transition analysis. α-Mangostin was found to suppress human colon HCT116 carcinoma cell proliferation with an LC₅₀ of 18.5 μM, inhibit the activity of cellular topos, halt cell cycle in the G2/M phase, and induce apoptosis. These results suggest that decreased proliferation by α-mangostin may be a result of the inhibition of cellular topos rather than pols, and α-mangostin might be an anticancer chemotherapeutic agent.

Distribution of Major Xanthones in the Pericarp, Aril, and Yellow Gum of Mangosteen (Garcinia MangostanaLinn.) Fruit and Their Contribution to Antioxidative Activity

Xanthone compounds in mangosteen (Garcinia mangostana Linn.) fruit have been reported to have biological activities including antioxidative and anti-inflammatory effects, and the major xanthone compounds in mangosteen are α-mangostin and γ-mangostin. The objectives of this research were to quantify and qualify the major xanthones in each part of the mangosteen fruit with and without yellow gum from the point of view of effective utilization of agricultural product. Quantitative evaluation revealed that yellow gum had extremely high amounts of α-mangostin and γ-mangostin (382.2 and 144.9 mg/g on a wet basis, respectively) followed by pericarp and aril. In mangosteen fruit with yellow gum inside, xanthones seemed to have shifted from the pericarp and to have concentrated in a gum on the surface of aril, and there was almost no difference between the amounts of α-mangostin and γ-mangostin in whole fruits with and without yellow gum. Pericarp and yellow gum showed much higher radical-scavenging activity and ferric reducing antioxidant potential than the aril.

A study on dispersion and characterisation of α-mangostin loaded pH sensitive microgel systems

Backgroundα-Mangostin was extracted with methanol from the rind of mangosteen fruit and purified by using silica gel column chromatography technique. The compound is characterised using infrared, 13C and 1H NMR as well as UV–vis spectroscopy. The α-mangostin dispersion in colloidal systems was studied by incorporating it with an ionic microgel, poly (N-Isopropylacrylamide)-co-2VP at different pH.ResultThe DLS result showed the size of microgel-α-mangostin mixture declined from 548 nm to 200 nm upon the increment of the pH. Moreover, it was found the morphology of loaded compound depended largely on the nature of the continuous phase of the microgel system. Interestingly, by manipulating the pH, α-mangostin tends to form crystal at extremely low pH and transforms into spherical shapes at pH 6.ConclusionThis research shows different structures of the α-mangostin particle that are attributed by adjusting the pH using microgel systems as a template.

Pharmacokinetic Properties of Pure Xanthones in Comparison to a Mangosteen Fruit Extract in Rats

The xanthones α-mangostin and γ-mangostin are the major bioactive compounds in Garcinia mangostana (mangosteen) fruit extracts. Previously, we reported the pharmacokinetic properties of α-mangostin in rats. The purpose of this follow-up study was to compare the pharmacokinetic characteristics of α-mangostin and γ-mangostin in rats if administered as either a pure compound or as a component of a mangosteen fruit extract. The absolute bioavailability of γ-mangostin when administered as a pure compound was determined by giving male Sprague Dawley rats 2 mg/kg γ-mangostin intravenously or 20 mg/kg orally. A 160 mg/kg aliquot of mangosteen fruit extract was administered, containing α- and γ-mangostin doses equal to 20 mg/kg and 4.5 mg/kg of each pure compound, respectively. Plasma samples were collected for both pharmacokinetic studies, and compound concentrations were measured by LC-MS/MS. The pharmacokinetic of γ-mangostin after intravenous administration followed a two-compartment body model. The half-life of the distribution phase was 2.40 min, and that of the elimination phase was 1.52 h. After oral administration, both α- and γ-mangostin underwent intensive first-pass metabolism, and both compounds were conjugated rapidly after oral administration. When given as an extract, the total absorption of α- and γ-mangostin was not increased, but the conjugation was slower, resulting in increased free (unconjugated) compound exposure when compared to pure compound administration. Since reported beneficial biological activities of mangosteen xanthones are based on the free, unconjugated compounds, food supplements containing mangosteen fruit extracts should be preferred over the administration of pure xanthones.

The harvest period of mangosteen fruit can be extended by chemical control of ripening—A proof of concept study

Mangosteen is an economically important crop in Southeast Asia. However, the harvest period of mangosteen fruit is rather short and effective methods to expand the harvest period and lessen the peak workload are desirable. We investigated the preharvest applications of ethephon or 1-methylcyclopropene (1-MCP) for their effects on harvest date, ethylene production, and mangosteen fruit quality. 1-MCP is available as tablets that we applied on fruit as a sprayed solution as well as by fumigation, respectively.The ripening of mangosteen fruit was significantly affected by the treatments, so that harvest date was advanced to an earlier time with ethephon and delayed to a later time by 1-MCP when using color development to guide harvest (at stage 0, pericarp uniformly yellowish-white or with a light green tinge or grayish spotting). The induced changes of harvest time are each of the order one to two weeks. The effectiveness of these chemicals is associated with the maturity stage of intact fruit. The increase period of ethylene production occurs concomitantly with unchanged fruit weight at its stationary phase of development. However, the ethylene production of harvested fruit was not affected by the treatments. The preharvest application of ethephon or 1-MCP, at climacteric maturity of fruit, has potential use in altering the harvest period of mangosteen products to earlier or later dates.

Abstract 3676: Selective modulation of CHOP/GADD153 in prostate cancer cells by alpha-mangostin promotes cell death.

Abstract Background: It is well-established that during endoplasmic reticulum (ER) stress cells utilize several cell signal pathways collectively named “unfolded protein reaction (UPR)” to re-establish homeostasis and promote cell survival. The upregulation of UPR proteins to an extent is thought to be a growth advantage for cancer cells. However, chronic ER stress or prolonged UPR will lead to apoptosis. Alpha-mangostin, a xanthone from mangosteen fruit, has been reported to effectively induce prostate cancer cell apoptosis in vitro and suppress xenograft tumor growth. Thus, we investigated the alteration of ER stress-related proteins in mangosteen fruit extract (MFE)- or α-Mangostin-treated prostate cancer cells as well as its correlation with apoptosis. Methods: Two human prostate cancer cell lines, 22Rv1 and LNCaP, and a prostate epithelial cell line were treated with MFE or α-mangostin. Flow cytometry, MTT and BrdU were used to evaluate cell apoptosis, viability and proliferation. Western blot and fluorescent microscopy were used to detect proteins involved in apoptosis or ER stress. We also evaluated the anti-cancer activity of MFE and α-mangostin in nude mice inoculated with 22Rv1 cells. In addition, pharmacokinetics data of α-mangostin was collected on wild type C57BL6 mice for toxicity concern. Results: MFE increased apoptosis, decreased viability and inhibited proliferation in prostate cancer cell lines. Both MFE and α-mangostin significantly upregulated the expression of ER stress proteins, such as PERK, CHOP and IRE1α. Both MFE and α-mangostin also effectively suppressed tumor growth in a xenograft tumor model without affecting body weight. Interestingly, CHOP knockdown enhanced apoptosis in α-mangostin-treated prostate cancer cells; both MFE and α-mangostin decreased PERK expression and did not induce ER stress in prostate epithelial cells (PrECs) from prostate cancer patients. Conclusions: Both MFE and α-mangostin selectively promote ER stress in prostate cancer cells and inhibit prostate cancer cell growth in a xenograft mouse model without observable toxicity, suggesting further research is needed to evaluate its potential as an anti-cancer agent. Citation Format: Gongbo Li, Sakina Petiwala, Dana Pierce, Jeremy Johnson. Selective modulation of CHOP/GADD153 in prostate cancer cells by alpha-mangostin promotes cell death. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 3676. doi:10.1158/1538-7445.AM2013-3676

α-Mangostin: Anti-Inflammatory Activity and Metabolism by Human Cells

Information about the anti-inflammatory activity and metabolism of α-mangostin (α-MG), the most abundant xanthone in mangosteen fruit, in human cells is limited. On the basis of available literature, we hypothesized that α-MG will inhibit the secretion of pro-inflammatory mediators by control and activated macrophage-like THP-1, hepatic HepG2, enterocyte-like Caco-2, and colon HT-29 human cell lines, as well as primary human monocyte-derived macrophages (MDM), and that such activity would be influenced by the extent of metabolism of the xanthone. α-MG attenuated TNF-α and IL-8 secretion by the various cell lines but increased TNF-α output by both quiescent and LPS-treated MDM. The relative amounts of free and phase II metabolites of α-MG and other xanthones present in media 24 h after addition of α-MG was shown to vary by cell type and inflammatory insult. Increased transport of xanthones and their metabolites across Caco-2 cell monolayers suggests enhanced absorption during an inflammatory episode. The anti-inflammatory activities of xanthones and their metabolites in different tissues merit consideration.

Quantitative Analysis of ?-Mangostin in Mangosteen Fruit Rind Extract (Deleted)

The paper has been deleted due to plagiarismThe original paper is published in Thai Journal of Agricultural Science 2009, 42 (1): 7-12 (www.thaiagj.org)

SUPERCRITICAL FLUID EXTRACTION OF α - MANGOSTIN FROM MANGOSTEEN FRUIT RIND (GARCINIA MANGOSTANA LINN.)

The extraction of α-mangostin from mangosteen fruit rind Garcinia mangostana Linn cultivated in Vietnam using supercritical carbon dioxide with ethanol as a modifier was studied in this work. Experimental design was used to investigate the effect of operating pressure (20-30MPa), temperature (313-333 K), and solvent flow rate (10-20g/min) on the recovery and the selectivity of α-mangostin. Statistical analysis of experiments indicated that pressure and flow rate of solvent affected on the recovery of α-mangostin; with the selectivity of α-mangostin, pressure, solvent flow rate, temperature and interaction between these factors significantly affected. The central composite design showed that the polynomial regression models were in good agreement with the experimental results with the coefficients of determination from 0.9037 to 0.9666. Based on the proposed model, the optimal condition for extraction that was within the experimental range was found to be at lowest temperature 313 K, highest pressure 30 MPa and the nearly lowest flow rate of solvent 12.71 g/min. It was proved that the model equation developed can be used for predicting the extraction of α-mangostin from Garcinia mangostana Linn. The maximum recovery and selectivity of α-mangostin achieved at the optimal conditions was 22.83 mg/g material and 32.77%.

The relation between the texture properties of mangosteen (Garcinia<br>mangostana Linn.) and the resonance frequency in detection of the<br>translucent and yellow gummy latex

A nondestructive measurement to predict an internal translucent disorder and yellow gummy latex in mangosteen fruit has proposed by using Vibration Frequency based on Strain gage Sensor (VFSS). This measurement was used vibration with frequency 0 – 50 Hz. The VFSS of 100 mangosteen samples were obtained an evaluation of various existed VFSS signal features based on time and frequency domains. From the experimental results, mass is the best comparing with the other property. This measurement can detect the yellow gummy latex in mangosteen at 35 Hz and 40 Hz.

Polyphenols from the mangosteen (Garcinia mangostana) fruit for breast and prostate cancer

The mangosteen (Garcinia mangostana) is a tropical fruit native to Southeast Asia and has long been reported to contain multiple health promoting properties. This fruit is an abundant source of xanthones, a class of polyphenolic compounds with a distinctive tricyclic aromatic ring system and is largely responsible for its biological activities including anti-cancer activity. Herein we describe the anti-cancer activity and mechanisms of mangosteen polyphenolic xanthones including α-Mangostin against breast cancer and prostate cancer. So far, extracts and individual xanthones have been found to induce apoptosis and inhibit proliferation on cancer cells in vitro and in vivo. Based on the reported findings there is clear evidence that these polyphenols target multiple signaling pathways involved in cell cycle modulation and apoptosis. Further work is required to understand its potential for health promotion and potential drug discovery for prostate and breast cancer chemoprevention.

Effects of Mangosteen Pericarp Extracts Against Mammary Cancer

The pericarp of the mangosteen fruit, Garcinia mangostana Linn, has a long history of use as a medicinal plant in Southeast Asia. The actions of mangosteen extracts have been scientifically supported and it has become a popular natural health-promoting dietary supplement. Mangosteen extracts, particularly α-mangostin, induced apoptosis via the mitochondrial pathway, cell cycle arrest by p21cip1 induction and Akt dephsophorylation in mammary cancer cells; these anti-proliferative effects are associated in vivo with suppression of tumor growth and metastasis in mouse mammary cancer models. Such preclinical evidence suggests that mangosteen extracts have potential chemotherapeutic and/or chemopreventive uses

Single Dose Oral Pharmacokinetic Profile of α-Mangostin in Mice

The mangosteen fruit (Garcinia mangostana) is a rich source of dietary xanthones with the most prominent being α-mangostin. Dietary xanthones have been reported to have a variety of health promoting properties. Until now, in vivo studies on the pharmacokinetic profile of α-mangostin are limited. For this study we employed an LC/MS/MS assay to determine the pharmacokinetic properties of α-mangostin suspension in cottonseed oil in C57BL/6 Mice. Mice were administered 100 mg/kg of α-mangostin by oral gavage and the plasma levels were analyzed over a 24 hour period. We observed the degree of exposure (i.e. area under the curve) of α-mangostin to be 5,736 nmol/L/hr and the maximum plasma concentration was 1,382 nmol/L. Furthermore, we provide evidence that α-mangostin undergoes glucuronidation into monoglucuronide and diglucuronide metabolites. Our study demonstrated that α-mangostin when administered in cotton seed oil to mice at a dose equivalent to 615 mg in a 90kg human adult achieves an approximate maximum plasma concentration of 1,300 nmol/L and is detectable for up to 24 hours. Further research is needed to understand the relationship between the pharmacokinetic properties of α-mangostin following oral administration and reported health benefits.

PENGARUH BERBAGAI PH SARI BUAH DAN SUHU PASTEURISASI TERHADAP AKTIVITAS ANTIOKSIDAN DAN TINGKAT PENERIMAAN SARI KULIT BUAH MANGGIS

ABSTRACTBackground: Oxidative stress is associated with the progression of degenerative disease. The consumption of antioxidant resources to prevent the body from oxidative stress damage. Mangosteen fruit hull is one of the mangosteen waste which has potential activity of natural antioxidant, such as xanthone and anthocyanins. Xanthon and anthocyanins influenced by pH and heating. Therefore, it is necessary to study about the effect of pH and temperature pasteurized on antioxidant activity of the mangosteen fruit hull juice.Objective : Analyze the effect of antioxidant activity and the level of acceptance of the mangosteen fruit hull juice with various pH and pasteurization temperature. Methods : An experimental study with a factorial design which combines pH (pH 3 and pH 4) and pasteurization temperature (temperature of 750C, 850C, 950C). The analyzes are antioxidant activities and the level of acceptance. The antioxidant activity obtained with DPPH (2,2 dhipenyl -1-pycrilhidrazyil) test. The acceptance test are conducted with hedonic test. Statistical analysis of the antioxidant activity using Two Way ANOVA test CI 95%, while the level of acceptance using Friedman test followed Wilcoxon test. Result : The result of antioxidant activity of mangosteen fruit hull juice ranged 80.64-89.70%. The various pH and pasteurization temperature did not effect the antioxidant activity of the mangosteen fruit hull juice. The results of test acceptance, color and taste are affected by variations in pH and temperature pasteurization, except aroma. The more acidic pH of juice, mangosteen fruit hull juice color of the panelists preferred. Acidification can not relieve harsh flavor mangosteen fruit hull juice. All mangosteen fruit hull juice aroma panelists preferred.Conclucion : The various pH and pasteurization temperature did not effect the antioxidant activity of the mangosteen fruit hull juice. The results of test acceptance, color and taste are affected by variations in pH and temperature pasteurization, except aroma. Keyword : antioxidant activity, mangosteen fruit hull juice, pH, pasteurization temperature

Postharvest technologies for mangosteen (Garcinia mangostana L.) conservation

The application of technologies to extend the postharvest life of mangosteen fruit was studied and compared to storage at 25 °C/70-75%R.H (25 °C control treatment). The fruits were packed in expanded polystyrene (EPS) trays (5 fruits/tray). Five treatments were carried out at 13 °C/ 90-95% RH: application of carnauba wax coating, lecithin + CMC (carboxymethyl cellulose) coating, 50 µm LDPE (low density polyethylene) film coating, 13 µm PVC (Polyvinyl chloride), and non-coated sample (13 °C control treatment). Physicochemical analyses were performed twice a week. A statistical design was completely randomized with 8 repetitions for each treatment plus the control treatment. The results were submitted to variance analysis, and the averages compared by the Tukey test at 5% probability. Among the quality parameters analyzed, more significant differences were observed for weight loss, texture, and peel moisture content. The results showed that the maximum storage period for mangosteen at 25 °C is two weeks; while storage at13 °C can guarantee the conservation of this fruit for 25 days. Therefore, the treatment at 13 °C/90-95% RH without the use of coatings and films was more effective and economical.

Neuroprotective effect of α-mangostin and curcumin against iodoacetate-induced cell death

Curcumin is a phenolic yellow curry pigment with anti-inflammatory and antioxidant activities and α-mangostin is a xanthone isolated from mangosteen fruit with antioxidant properties. Iodoacetate (IAA) is an inhibitor of the glycolytic enzyme glyceraldehyde-3-phosphate dehydrogenase that induces a model of metabolic inhibition in neurons where reactive oxygen species (ROS) production is a significant mechanism. Furthermore, it has been shown that the induction of heme oxygenase-1 (HO-1) protects against IAA-induced neuronal death.ObjectivesTo study the effects of α-mangostin and curcumin against the IAA-induced cell death and on HO-1 expression in primary cultures of cerebellar granule neurons (CGNs).MethodsCGNs were treated with curcumin or α-mangostin before the addition of IAA. Cell viability and ROS production were measured 24 and 4 hours after IAA addition, respectively. HO-1 expression was measured by western blot.ResultsBoth α-mangostin and curcumin pretreatment ameliorated the neuronal death induced by IAA in a concentration-dependent way, which was associated with an amelioration of IAA-induced ROS formation. In addition, it was found that α-mangostin and curcumin induced HO-1 expression.DiscussionTreatment with α-mangostin and curcumin provided a neuroprotective effect against IAA in primary cultures of CGNs, an effect associated with an amelioration of the IAA-induced ROS production. HO-1 induced by these antioxidants may also be involved in the neuroprotective effect. Future work will be required to determine whether α-mangostin may cross the blood–brain barrier and achieve enough bioavailability to elicit a protective response in the brain being an effective nutraceutical compound for preventive therapy of neurodegenerative diseases.

Quantification of α-, β- and γ-mangostin in Garcinia mangostana fruit rind extracts by a reverse phase high performance liquid chromatography

Garcinia mangostana fruit rinds contain high concentration of xanthones such as α-, and γ-mangostin. The α-mangostin-rich extracts have been used widely in nutritional supplements, herbal cosmetics and pharmaceutical preparations. This study aims to develop a reverse phase HPLC method for the quantification of α-, β- and γ-mangostin in G. mangostana fruit rind extracts. The method was validated at 244, 254, 316 and 320 nm. Selectivity was determined by comparing the retention time and the UV-Vis spectra of α-, β- and γ-mangostin in G. mangostana extracts with those of the reference compounds. Linearity was in the range 0.2 to 200 µg/ml at R2 > 0.9999. The intraday and interday precision was determined as a relative standard deviation, and was found to be (0.4±0.4) and (0.3 ± 0.3)%, respectively. The percentage recovery was in the range (96.3 ± 2.5) to (100.5 ± 3.4)%. The limits of detection and quantification were in the range 0.06 to 0.12 and 0.14 to 0.37 µg/ml, respectively. The reported method was applied for the determination of α-, β- and γ-mangostin concentration in 7 extracts of G. mangostana fruit rinds, and it could be considered as an important analytical tool for quality control, stability studies, pharmacokinetics, and standardization purposes. Key words: Alpha-, beta-, and gamma-mangostin, Garcinia mangostana, mangosteen.

Abstract 2574: Mangosteen fruit extract promotes endoplasmic reticulum stress through upregulation of CHOP/GADD153 in prostate cancer cells

Abstract Background: The mangosteen fruit (Garcinia mangostana) is native to Southeast Asia and has been reported to contain a variety of health promoting properties that include antioxidant, anti-inflammatory, anti-microbial and anti-diabetic activities. The principle constituents isolated from the mangosteen fruit are the xanthones with over 50 unique entities isolated to date. Prostate cancer (PCa) is the second most common cancer-related death in adult males and is ideal for evaluating promising cancer preventive agents because it develops at old age and is usually asymptomatic until advanced. This suggests that even a slight delay in the diagnosis of prostate cancer could have a profound public health impact. In our current study, we investigated the anticancer effects of a highly characterized mangosteen fruit extract on PCa cell lines to understand the mechanism of endoplasmic reticulum stress. Next, we evaluated the anticancer activity of mangosteen fruit extract in an athymic nude mouse model. Methods: Two human prostate cancer cell lines, 22Rv1 and LNCaP, were treated with a standardized mangosteen fruit extract. Flow cytometry, MTT, BrdU, and siRNA were used to evaluate cell apoptosis, cell viability and cell proliferation. Whole cell lysates were used to detect protein expression changes of androgen receptor (AR), pro-apoptotic protein Bax and other proteins involved in cell cycle or ER stress following treatment with mangosteen fruit extract. Next, we evaluated mangosteen fruit extract for anti-cancer activity in Athymic (nu/nu) nude mice inoculated with 22Rv1 cells. These mice received either mangosteen fruit extract or vehicle. In addition, a pharmacokinetics assay of mangosteen fruit extract, complete blood count (CBC), and serum biochemistry were performed on wild type C57BL6 mice for possible toxicity. Results: Our results demonstrate that mangosteen fruit extract effectively induced apoptosis, decreased cell viability and inhibited cell proliferation in multiple prostate cancer cell lines. Mangosteen fruit extract treatment induced a dose-dependent AR down-regulation and Bax up-regulation, induced G1 cell cycle arrest, and significantly increased the expression of ER stress proteins, such as PERK, CHOP and IRE1 in PCa cells. In addition, mangosteen fruit extract treatment significantly suppressed tumor growth in a xenograft tumor model and did not alter body weight, complete blood count or serum biochemistry in normal mice. Conclusion: Our results demonstrate that mangosteen fruit extract upregulated the ER stress proteins CHOP, PERK and IRE1. Mangosteen fruit extract treatment effectively suppressed PCa cell growth in a xenograft mouse model without obvious toxicity, suggesting further research is needed to determine its potential as a cancer preventive and/or therapeutic agent. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 2574. doi:1538-7445.AM2012-2574