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Alpha-mangostin is the major component in Mangosteen (Garcinia mangostana Linn) pericarp having severalpharmacological activities including reducing blood pressure, antidiabetic, anticancer, and antioxidants. The objectiveof this study was to develop Fourier transform infrared spectroscopy-multivariate calibration of partial least square(PLS) for quantitative analysis of alpha-mangostin and to classify mangosteen pericarp using principal componentanalysis. Mangosteen pericarps from different locations (Java provinces and South Sulawesi, Republic of Indonesia)were extracted using ethanol and were subjected to high performance liquid chromatography (HPLC) for the analysisof alpha-mangostin and Fourier transform infrared (FTIR) spectroscopy measurements. HPLC was used to determinethe levels of alpha-mangostin and used as actual values during FTIR spectroscopy analysis. The prediction of alphamangostin was obtained from the correlation between actual values and FTIR predicted values and facilitated withthe PLS model. The results showed that the wavenumbers region of 3,825–937 cm−1 offered a reliable model with acoefficient correlation (r) value of 0.9927 and root mean square error of calibration of 0.0831%. The validation modelsalso exhibited the accurate and precise results for the prediction of alpha-mangostin with an r-value of 0.9754 androot mean square error of prediction value of 0.174%. Furthermore, the chemometrics of principal component analysisusing variables of absorbances at selected fingerprint (1,000–800 cm−1) could classify mangosteen pericarp fromdifferent regions. FTIR spectroscopy combined with chemometrics offered a reliable method for quality assurance ofmangosteen pericarp
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Objective: To investigate the antibiofilm activity of alpha-mangostin (AMG) loaded nanoparticle (nanoAMG) against dental caries pathogen Streptococcus mutans. Methods: AMG was isolated from the peels of Garcinia mangostana L. using silica gel columns and chemically analysed by high performance liquid chromatography and nuclear magnetic resonance. NanoAMG was prepared using the solvent evaporation method combined with high-speed homogenization. The nanoparticles were characterized using dynamic light scattering, field emission scanning electron microscopy (FE-SEM) and Fourier transform infrared spectroscopy (FTIR). The toxicity of nanoAMG in fibroblast NIH/3T3 cell line was determined using MTT method. The antibiofilm effect of nanoAMG was determined through the evaluation of biofilm formation by Streptococcus mutans using a 96-well plate. Biofilm biomass was quantified using crystal violet. Cell viability was observed under confocal microscopy using LIVE/DEAD BacLight staining. Moreover, gene expression was determined by quantitative real-time PCR and membrane permeabilization activity by measuring the uptake of o-nitrophenol-β-D-galactoside. Results: NanoAMG size was in a range of 10-50 nm with a polydispersity index of < 0.3 and zeta potential value of -35.2 mV. The size and the incorporation of AMG in the nanoparticles were confirmed by FE-SEM and FTIR analyses. The IC50 values of the test agents on NIH/3T3 cells were (9.80 ± 0.63) μg/mL for AMG and (8.70 ± 0.81) μg/mL for nanoAMG, while no toxicity was generated from excipients used to prepare nanoparticles. In the early stage of biofilm formation, treatment with 6.25 μmol/L nanoAMG caused a reduction in biofilm biomass up to 49.1％, compared to 33.4％ for AMG. In contrast, biofilms at the late stage were more resistant to the test agents. At 96 μmol/L (= 10 × MIC), nanoAMG reduced only 20.7％ of biofilm biomass while AMG did not show any effect. Expressions of gtfB and gtfC genes involved in biofilm formation were down-regulated 3.3 and 12.5 folds, respectively, compared to AMG (2.4 and 7.6 folds, respectively). LIVE/DEAD BacLight fluorescence staining and microscopy observation indicated that biofilm cells were killed by both nanoAMG andAMG at 48 μmol/L (= 5 × MIC). In addition, membrane permeabilization activity was increased in a time dependent manner and higher in nanoAMG treated cells compared toAMG.Conclusions: AMG coated nanoparticle can enhance AMG bioactivity and can be used as a new and promising antibiofilm agent.
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Objective: To investigate the antibiofilm activity of alpha- mangostin (AMG) loaded nanoparticle (nanoAMG) against dental caries pathogen Streptococcus mutans. Methods: AMG was isolated from the peels of Garcinia mangostana L. using silica gel columns and chemically analysed by high performance liquid chromatography and nuclear magnetic resonance. NanoAMG was prepared using the solvent evaporation method combined with high-speed homogenization. The nanoparticles were characterized using dynamic light scattering, field emission scanning electron microscopy (FE-SEM) and Fourier transform infrared spectroscopy (FTIR). The toxicity of nanoAMG in fibroblast NIH/3T3 cell line was determined using MTT method. The antibiofilm effect of nanoAMG was determined through the evaluation of biofilm formation by Streptococcus mutans using a 96-well plate. Biofilm biomass was quantified using crystal violet. Cell viability was observed under confocal microscopy using LIVE/DEAD BacLight staining. Moreover, gene expression was determined by quantitative real-time PCR and membrane permeabilization activity by measuring the uptake of o-nitrophenol- β-D-galactoside. Results: NanoAMG size was in a range of 10-50 nm with a polydispersity index of < 0.3 and zeta potential value of -35.2 mV The size and the incorporation of AMG in the nanoparticles were confirmed by FE-SEM and FTIR analyses. The IC
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ABSTRACT Stingless bees (Apoidea) are widely distributed and commercially cultivated in artificial hives in fruit gardens. Their propolis are commonly used in traditional medicine to treat various diseases (e.g., abscesses, inflammations, and toothaches) and as a constituent of numerous health products. Thus, this study aimed to (i) develop and validate a high-performance thin layer chromatography method for the quantitation of major active constituents (α- and γ-mangostins) in propolis produced by five stingless bee species (Tetragonula fuscobalteata Cameron, T. laeviceps Smith, T. pagdeni Schwarz, Lepidotrigona terminata Smith, and L. ventralis Smith) cultivated in Thai mangosteen orchards and (ii) determine an optimal extraction solvent. Separation was performed on a silica gel 60 F254 plate using toluene/ethyl acetate/formic acid (8:2:0.1, v/v/v) as a mobile phase, and the developed method was validated to assure its linearity, precision, accuracy, and limits of detection/quantitation. Propolis extract from T. fuscobalteata exhibited the highest mangostin content, and acetone was shown to be more a more effective extraction solvent than dichloromethane, ethanol, or methanol. Thus, the simplicity and reliability of the developed method make it well suited for the routine analysis (e.g., for quality control) of commercial products containing stingless bee propolis.
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Objective: This study assessed the effects of alpha-mangostin (AM) and citronella oil (CO) working alone or in combination against Propionibacterium acnes (P. acnes) and Staphylococcus aureus (S. aureus). Methods: The screening for antibacterial activity of AM and CO against P. acnes and S. aureus was carried out using the disk diffusion method. The minimum inhibitory concentrations (MICs) and minimum bactericidal concentrations (MBCs) of these two substances were determined using the broth microdilution method. The fractional inhibitory concentration indices (FICI) of a combination of AM and CO were obtained by checkerboard dilution assay. Results: The results showed that alpha-mangostin and citronella oil do indeed fight against P. acnes and S. aureus. The MICs and MBCs of AM against P. acnes and S. aureus were the same at 6.25 and 50 µg/ml, respectively. Both the MIC and the MBC of CO against P. acnes were 27.81µg/ml. The MIC and the MBC of CO against S. aureus were 112.13 and 224.25 µg/ml, respectively. The FICI of a combination of AM and CO against P. acnes and S. aureus were 2.00, indicating indifferent interaction with no additional inhibitory effect. Conclusion: AM and CO are very effective against P. acnes and S. aureus, nevertheless their effect when used together was indifferent from using alone. Further research may find that either or both of these substances combined with yet a different natural agent could provide synergy againstP. acnes and S. aureus.
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Objective: To evaluate the synergistic effect of α-mangostin with tetracycline, erythromycin, and clindamycin against bacteria involved in acne production. Methods: A broth microdilution method was used to determine the minimum inhibitory concentration (MIC) of α-mangostin and a range of antibiotics. Synergistic effects on antibacterial activity were determined based on their own MIC, and then using a checkerboard method and a time-kill assay at 37 °C for 24 h. Results: α-Mangostin exhibited antibacterial activity against Propionibacterium acnes, Staphylococcus aureus, S. epidermidis and S. pyogenes with MIC values of 0.78, 3.13, 0.78, and 6.25 µg/mL, respectively. The results of the checkerboard assay showed that α-mangostin produced synergistic effects with tetracycline, erythromycin, and clindamycin against all tested bacteria, with a fractional inhibitory concentration index (FICI) between 0.09 and 0.32. Moreover, time-kill curve data indicated that α-mangostin increased the antibacterial activity of tetracycline, erythromycin, and clindamycin. Conclusion: These findings suggested that α-mangostin may be used to enhance the antibacterial activity of some antibiotics against bacteria involved in acne production.
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Objective To investigate the possible molecular mechanism for alpha(α)-mangostin's inhibition of the proliferation and apoptosis of human gastric cancer cells.Methods Human gastric adenocarcinoma SGC7901 cell line was treated with α-mangostin.CCK8 method was used to measure the viability of SGC7901 cells.The effect of α-mangostin on apoptosis and cell cycle was determined by immune fluorescence and flow cytometry.The expression of the relevant proteins was detected using Western blot.The shapiro-wilk test was performed for evaluation of deviation from normality.Normally distributed data was analyzed with one-way ANOVA.Welch test was used in data with heterogeneity of variance and multiple compared by Games-Howell test after that.Results CCK8 results showed that cell viability differed significantly among groups treated with different concentrations of α-mangostin(10,15,20,25,and 30 μmol/L)(P＜0.05).QPCR data showed that the concentration of α-mangostin was positively correlated with mRNA level of LC 3 but not caspase protein(r=0.976,P＜0.05).In 15 μmol/L but not 10 μmol/L α-mangostin treatment system,the autophagy inhibitors 3-MA(10 μmol/L),bafilomycin A(10 μmol/L)and LY294002(10 μmol/L)could significantly alleviate α-mangostin's killing effect on SGC7901 cells(P＜0.05).Conclusion The anti-tumor effects of α-mangostin against human gastric adenocarcinoma cells in vitro can be partly attributed to apoptosis,autophagy and arresting cell phase.
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Objective: To find new compounds in order to overcome the mainstay of metastatic breast cancer due to the adverse side effects from, and increasing resistance to, current chemotherapeutic agents. Methods: α-Mangostin and apigenin were reported in comparison to doxorubicin, a chemotherapeutic drug. Ductal carcinoma (BT474) cell line and non-tumorigenic epithelial tissue from mammary gland (MCF-10A) were used. Cell viability assessment was calculated by the standard 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide method. Cell morphology was investigated by light microscopy. By flow cytometry analysis, programmed cell death was observed using annexin Ⅴ and propidium iodide staining while cell-cycle arrest was observed using propidium iodide staining. Change in transcriptional expression was evaluated by real-time quantitative reverse transcription PCR. Results: In 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, the result revealed α-mangostin and apigenin were more cytotoxic to BT474 cells. Longer exposure times to α-mangostin and apigenin caused more floating cells and a lower density of adhered cells with more vacuoles present in the colonies in BT474 only. α-Mangostin and apigenin caused necrosis in BT474 cells in a 24 h exposure, but a small amount of early apoptotic cells could also be detected at 24, 48 and 72 h exposure, whereas doxorubicin caused early apoptosis to BT474 cells at 24 h. Transcript expression and activity analysis supported caspase-3 was involved in the death of BT474 cells treated by all compounds. Moreover, α-mangostin and apigenin arrested the cell-cycle at the G1-phase, but at the G2/M-phase by doxorubicin. All three compounds induced a change in transcript expression levels of inflammation-associated, proto-oncogene, autophagy-associated and apoptosis-associated genes. Conclusions: α-Mangostin and apigenin are worth investigating as potential new sources of chemotherapeutic agents for breast cancer treatment.
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AIM To analyze the effects of α-mangostin on the proliferation and apoptosis of osteoarthritis (OA) chondrocytes.METHODS Human OA chondrocytes were isolated and then treated with 5,10 or 20 μmol/L α-mangostin.24,48 or 72 h after the treatment,the cell proliferation was measured by MTT assay,and the cell apoptosis was detected by flow cytometry.The expression check on MMP-1,MMP-3,MMP-13,PPARγ,PPARδ,PGC-lα and TNF-α was accomplished by Western blot.The contents of collagen-Ⅱ,PG,IL-1β and IL-6 were tested by ELISA.RESULTS α-Mangostin significantly induced cell proliferation and suppressed cell apoptosis,and it significantly increased the production of collagen-Ⅱ and PG,decreased the expressions of MMP-1,MMP-3 and MMP-13,induced the expressions of PPARγ,PPARδ and PGC-1α,and decreased the expression of TNF-α.Furthermore,α-mangostin significantly inhibited the production of IL-1β and IL-6.CONCLUSION α-Mangostin attenuates the destruction and degradation of cartilago articularis by inducing OA chondrocytes proliferation,inhibiting cell apoptosis and inflammation,and increasing expressions of PPARγand PPARδ.
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Objective: To find new compounds in order to overcome the mainstay of metastatic breast cancer due to the adverse side effects from, and increasing resistance to, current chemotherapeutic agents. Methods: α-Mangostin and apigenin were reported in comparison to doxorubicin, a chemotherapeutic drug. Ductal carcinoma (BT474) cell line and non-tumorigenic epithelial tissue from mammary gland (MCF-10A) were used. Cell viability assessment was calculated by the standard 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide method. Cell morphology was investigated by light microscopy. By flow cytometry analysis, programmed cell death was observed using annexin V and propidium iodide staining while cell-cycle arrest was observed using propidium iodide staining. Change in transcriptional expression was evaluated by real-time quantitative reverse transcription PCR. Results: In 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, the result revealed α-mangostin and apigenin were more cytotoxic to BT474 cells. Longer exposure times to α-mangostin and apigenin caused more floating cells and a lower density of adhered cells with more vacuoles present in the colonies in BT474 only. α-Mangostin and apigenin caused necrosis in BT474 cells in a 24 h exposure, but a small amount of early apoptotic cells could also be detected at 24, 48 and 72 h exposure, whereas doxorubicin caused early apoptosis to BT474 cells at 24 h. Transcript expression and activity analysis supported caspase-3 was involved in the death of BT474 cells treated by all compounds. Moreover, α-mangostin and apigenin arrested the cell-cycle at the G
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OBJECTIVE@#To isolate α-mangostin (AMG) from the peels of mangosteen (Garcinia mangostana L.), grown in Vietnam, and to investigate antibiofilm activity of this compound against three Staphylococcus aureus (S. aureus) strains, one of which was methicillin-resistant S. aureus (MRSA) and the other two strains were methicillin-sensitive S. aureus (MSSA).@*METHODS@#AMG in n-hexane fraction was isolated on a silica gel column and chemically analyzed by HPLC and NMR. The antibiofilm activity of this compound was investigated by using a 96-well plate model for the formation of biofilms. Biofilm biomass was quantified using crystal violet. The viability of cells was observed under confocal microscopy using LIVE/DEAD BacLight stains. Biofilm composition was determined using specific chemical and enzyme tests for polysaccharide, protein and DNA. Membrane-damaging activity was assayed by measuring the hemolysis of human red blood cells in presence of AMG.@*RESULTS@#The results indicated that the isolated AMG, with a purity that exceeded 98%, had minimal inhibitory concentrations in the range of 4.6-9.2 μmol/L for the three strains tested. Interestingly, the MSSA strains were more sensitive to AMG than the MRSA strain. Minimal bactericidal concentrations were 2-fold higher than the minimal inhibitory concentration values for the three strains, indicating that AMG was a bactericidal compound. AMG also prevented biofilm formation effectively, albeit that again the MRSA strain was the most resistant. Interestingly, biofilms of the MRSA strain contained protein as a main component of the extracellular matrix, whereas this was polysaccharide in the MSSA strains. This might relate to the resistance of the MRSA 252 strain to AMG. Assays using human red blood cells indicated that AMG caused significant membrane damage with 50% of cell lysis occurred at concentration of about 36 μmol/L.@*CONCLUSIONS@#Our results provide evidence that the isolated AMG has inhibitory activity against biofilm formation by S. aureus, including MRSA. Thus, isolated AMG proposes a high potential to develop a novel phytopharmaceutical for the treatment of MRSA.
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Objective To isolate α-mangostin (AMG) from the peels of mangosteen (Garcinia mangostana L.), grown in Vietnam, and to investigate antibiofilm activity of this compound against three Staphylococcus aureus (S. aureus) strains, one of which was methicillin-resistant S. aureus (MRSA) and the other two strains were methicillin-sensitive S. aureus (MSSA). Methods AMG in n-hexane fraction was isolated on a silica gel column and chemically analyzed by HPLC and NMR. The antibiofilm activity of this compound was investigated by using a 96-well plate model for the formation of biofilms. Biofilm biomass was quantified using crystal violet. The viability of cells was observed under confocal microscopy using LIVE/DEAD BacLight stains. Biofilm composition was determined using specific chemical and enzyme tests for polysaccharide, protein and DNA. Membrane-damaging activity was assayed by measuring the hemolysis of human red blood cells in presence of AMG. Results The results indicated that the isolated AMG, with a purity that exceeded 98%, had minimal inhibitory concentrations in the range of 4.6–9.2 μmol/L for the three strains tested. Interestingly, the MSSA strains were more sensitive to AMG than the MRSA strain. Minimal bactericidal concentrations were 2-fold higher than the minimal inhibitory concentration values for the three strains, indicating that AMG was a bactericidal compound. AMG also prevented biofilm formation effectively, albeit that again the MRSA strain was the most resistant. Interestingly, biofilms of the MRSA strain contained protein as a main component of the extracellular matrix, whereas this was polysaccharide in the MSSA strains. This might relate to the resistance of the MRSA 252 strain to AMG. Assays using human red blood cells indicated that AMG caused significant membrane damage with 50% of cell lysis occurred at concentration of about 36 μmol/L. Conclusions Our results provide evidence that the isolated AMG has inhibitory activity against biofilm formation by S. aureus, including MRSA. Thus, isolated AMG proposes a high potential to develop a novel phytopharmaceutical for the treatment of MRSA.
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5-fluorouracil (5-FU) is a chemotherapeutic agent commonly used for treatment of solid tumors, including colorectal cancer. However, chemoresistance against 5-fluorouracil (5-FU) often limits its success for chemotherapy and, therefore, finding out appropriate adjuvant(s) that might overcome chemoresistance against 5-FU bears a significant importance. In the present study, we have found that α-mangostin can sensitize 5-FU-resistant SNUC5/5-FUR colon cancer cells to apoptosis. Exposure of α-mangostin induced significant DNA damages and increased the intracellular 8-hydroxyguanosine (8-OH-G) and 4-hydroxynonenal (4-HNE) levels in SNUC5 and SNUC5/5-FUR cells. Western blot analysis illustrated that α-mangostin-induced apoptosis was mediated by the activation of the extrinsic and intrinsic pathways in SNUC5/5-FUR cells. In particular, we observed that Fas receptor (FasR) level was lower in SNUC5/5-FUR cells, compared with SNUC5 cells and that silencing FasR attenuated α-mangostin-mediated apoptosis in SNUC5/5-FUR cells. Together, our study illustrates that α-mangostin might be an efficient apoptosis sensitizer that can overcome chemoresistance against 5-FU by activating apoptosis pathway.
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Receptor fas , Apoptosis , Western Blotting , Colon , Neoplasias del Colon , Neoplasias Colorrectales , Daño del ADN , Quimioterapia , FluorouraciloRESUMEN
Inflammation plays an important role in host defense against external stimuli such as infection by pathogen, endotoxin or chemical exposure by the production of the inflammatory mediators that produced by macrophage. Anti-inflammatory factor is important to treat the dangers of chronic inflammation associated with chronic disease. This research aims to analyze the anti-inflammatory effects of Garcinia mangostana L. peel extract (GMPE), α-mangostin, and γ-mangostin in LPS-induced murine macrophage cell line (RAW 264.7) by inhibiting the production of inflammatory mediators. The cytotoxic assay of G. mangostana L. extract, α-mangostin, and γ-mangostin were performed by MTS (3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium) to determine the safe and non-toxic concentration in RAW 264.7 for the further assay. The concentration of inflammatory mediators (COX-2, IL-6, and IL-1β) were measured by the ELISA-based assay and NO by the nitrate/nitrite colorimetric assay in treated LPS-induced RAW 264.7 cells. The inhibitory activity was determined by the reducing concentration of inflammatory mediators in treated LPS-induced RAW 264.7 over the untreated cells. This research revealed that GMPE, α-mangostin, and γ-mangostin possess the anti-inflammatory effect by reducing COX-2, IL-6, IL-1β, and NO production in LPS-induces RAW 264.7 cells.
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Línea Celular , Enfermedad Crónica , Fibrinógeno , Garcinia mangostana , Inflamación , Interleucina-6 , MacrófagosRESUMEN
The methanol, ethyl acetate and petroleum ether crude extracts of mangosteen pericarp and α- mangostin were evaluated for the antioxidant capacity and tyrosinase inhibition properties. The ferric reducing antioxidant power (FRAP) assay was used to investigate their antioxidant capacity. Tyrosinase inhibition effect was evaluated using mushroom tyrosinase inhibition assay. Methanol extract has higher antioxidant reducing capacity (m= 1.621), compared to the rest of the extracts. Meanwhile, ethyl acetate extract and α- mangostin showed potent tyrosinase inhibition activities as compared to Kojic acid, a well- known tyrosinase inhibitor. It is observed that tyrosinase inhibition effect is antioxidant independent as ethyl acetate extract possessed low antioxidant capacity. This study suggests direct tyrosinase inhibition by ethyl acetate extract of Garcinia mangostana.
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AlM:To discuss the protective effect ofα-mangostin on retinal light damage in mice.METHODS:Totally 30 Balb/c mice, aged 6~8wk, were randomly divided into the control group, light-exposure group and α-mangostin group. Every group contained 10 mice. Mice of α-mangostin group were treated with alpha-mangostin at the dose of 30mg/( kg · d ) body weight by intragastric administration daily for 7d, and then exposed to white light at the 5th d. The light-exposure group and α-mangostin group were exposed to 5 000 ± 200lx white light-emmiting diodes (LEDs) for continuously 1h to establish the mice model of retinal light damage. Flash -electroretinograme was recorded 72h after light exposure. The changes in retinal morphology of mice were observed by light microscopy. Retinas were extracted to detect the malondialdhyde ( MDA ) content change of the retinal homogenate.RESULTS: Flash-electroretinogram ( F-ERG ) showed that retinal dysfunction was less severe in α-mangostin group than in light-exposure group ( P<0. 05 ). Light microscopy test showed that retina structural damage was less severe in α-mangostin group than in light-exposure group (P<0. 05). The level of MDA in retinal tissue of α-mangostin group was significantly lower when compared with light-exposure group (P<0. 05).CONCLUSlON: α-mangostin inhibits lipid peroxidation induced by light damage and protect retina against light damage.
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A sunscreen active compound has been isolated from the ethanol extract of Garcinia mangostana Linn (Clusiaceae). The ethanol extract was fractionated by liquid liquid extraction with n-hexane, methylene chloride and ethyl acetate, followed by further fractionation and purification using column chromatography on silica gel and gradient elution with combinations of n-hexane and ethyl acetate. Isolation and fractionation was guided by sunscreen activity assay. One of the active compounds was identified as αmangostin based on LC-MS and NMR Spectroscopy. The SPF value of the isolated α –mangostin at 50 and 100 ppm were 21.76 and 37.18, respectively and were much higher than the SPF values of the fractions obtained by liquid-liquid extraction.
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alpha-Mangostin is a xanthon derivative contained in the fruit hull of mangosteen (Garcinia mangostana L.), and the administration of alpha-Mangostin inhibited the growth of transplanted colon cancer, Her/CT26 cells which expressed Her-2/neu as tumor antigen. Although alpha-Mangostin was reported to have inhibitory activity against sarco/endoplasmic reticulum Ca2+ ATPase like thapsigargin, it showed different activity for autophagy regulation. In the current study, we found that alpha-Mangostin induced autophagy activation in mouse intestinal epithelial cells, as GFP-LC3 transgenic mice were orally administered with 20 mg/kg of alpha-Mangostin daily for three days. However, the activation of autophagy by alpha-Mangostin did not significantly increase OVA-specific T cell proliferation. As we assessed ER stress by using XBP-1 reporter system and phosphorylation of eIF2alpha, thapsigargin-induced ER stress was significantly reduced by alpha-Mangostin. However, coadministration of thapsigargin with alpha-Mangostin completely blocked the antitumor activity of alpha-Mangostin, suggesting ER stress with autophagy blockade accelerated tumor growth in mouse colon cancer model. Thus the antitumor activity of alpha-Mangostin can be ascribable to the autophagy activation rather than ER stress induction.
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Animales , Ratones , Autofagia , ATPasas Transportadoras de Calcio , Proliferación Celular , Neoplasias del Colon , Células Epiteliales , Frutas , Garcinia mangostana , Ratones Transgénicos , Fosforilación , Reticulum , Tapsigargina , Trasplantes , XantonasRESUMEN
This study aimed to investigate the antitumorigenicity of xanthones-rich extract from Garcinia mangostana L., Clusiaceae, fruit rinds which was obtained by a simple recrystallization of 75 percent ethanolic extract. α-Mangostin content of the extract was determined qualitatively by TLC and quantitatively by HPLC, and total xanthones content was quantified by UV spectrophotometry. The extract was evaluated for cytotoxicity, apoptosis and antitumorigenicity on HCT 116 human colorectal carcinoma cells. α-Mangostin was found to be the main constituent of the extract which was 71.2±0.1 percent, and the total xanthones content was 95±4.8 percent (wt/wt). The extract showed potent dose dependent cytotoxicity with IC50 value 9.2 μg/mL. Apoptosis studies revealed activation of caspases 3 and 7, DNA fragmentation, chromatin condensation and loss of mitochondrial membrane potential. Studies on cell migration and colony formation indicate reduced cell migration ability and clonogenicity of treated HCT 116 cells at sub-inhibitory concentrations. Taken together, the cytotoxic effect of the xanthones extract is mediated through the mitochondrial pathway of apoptosis. The reduced cell migration and clonogenicity of HCT 116 cells might prevent both primary and metastatic tumor growth in vivo which will be the topic of our future work using the metastatic orthotopic colon cancer model.