AIM:To investigate the effect of α-mangostin on the growth and apoptosis induction of human colon cancer cells.METHODS:The three colorectal adenocarcinoma cell lines tested (COLO 205,MIP-101 and SW 620) were treated ...AIM:To investigate the effect of α-mangostin on the growth and apoptosis induction of human colon cancer cells.METHODS:The three colorectal adenocarcinoma cell lines tested (COLO 205,MIP-101 and SW 620) were treated with α-mangostin to determine the effect on cell proliferation by MTT assay,cell morphology,chromatin condensation,cell cycle analysis,DNA fragmentation,phosphatidylserine exposure and changing of mitochondrial membrane potential.The molecular mechanisms of α-mangostin mediated apoptosis were further investigated by Western blotting analysis including activation of caspase cascade,cytochrome c release,Bax,Bid,p53 and Bcl-2 modifying factor.RESULTS:The highest inhibitory effect of α-mangostin on cell proliferation of COLO 205,MIP-101 and SW 620 were 9.74 ± 0.85 μg/mL,11.35 ± 1.12 μg/mL and 19.6 ± 1.53 μg/mL,respectively.Further study showed that α-mangostin induced apoptotic cell death in COLO 205 cells as indicated by membrane blebbing,chromatin condensation,DNA fragmentation,cell cycle analysis,sub-G1 peak (P < 0.05) and phosphatidylserine exposure.The executioner caspase,caspase-3,the initiator caspase,caspase-8,and caspase-9 were expressed upon treatment with α-mangostin.Further studies of apoptotic proteins were determined by Western blotting analysis showing increased mitochondrial cytochrome c release,Bax,p53 and Bmf as well as reduced mitochondrial membrane potential (P < 0.05).In addition,up-regulation of tBid and Fas were evident upon treatment with α-mangostin (P < 0.01).CONCLUSION:α-Mangostin may be effective as an anti-cancer agent that induced apoptotic cell death in COLO 205 via a link between extrinsic and intrinsic pathways.展开更多
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: 毩-Mangostin...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: 毩-Mangostin and apigenin were reported in comparison to doxorubicin, a chemotherapeutic drug. Ductal carcinoma(BT474) cell line and nontumorigenic epithelial tissue from mammary gland(MCF-10 A) 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 observed using propidium iodide st桋 and propidium iodide staining while cell-cycle arrest wasaining. 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 and apigenin were more cytotoxic to BT474 cells. Longer exposure times to 毩-mangostin enin caused more floating cells and a lower density of adhered cells wi毩-mangostin and apigth more vacuoles present in the colonies in BT474 only. 毩-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, 毩-mangostin and apigenin arrested the cellcycle 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, autophagyassociated and apoptosis-associated genes. Conclusions: ntial new sources of chemotherapeuti毩-Mangostin and apigenin are worth investigating as potec agents for breast cancer treatment.展开更多
Objective: To isolate a-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) st...Objective: To isolate a-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 methicillinsensitive 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 Bac Light stains. Biofilm composition was determined using specific chemical and enzyme tests for polysaccharide, protein and DNA. Membranedamaging 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 mmol/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 mmol/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.展开更多
Objective:To evaluate the synergistic effect ofα-mangostin with tetracycline,erythromycin,and clindamycin against bacteria involved in acne production.Methods:A broth microdilution method was used to determine the mi...Objective:To evaluate the synergistic effect ofα-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)ofα-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 for24 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 6.25μg/m L,respectively.The results of the checkerboard assay showed thatα-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 thatα-mangostin increased the antibacterial activity of tetracycline,erythromycin,and clindamycin.Conclusion:These findings suggested thatα-mangostin may be used to enhance the antibacterial activity of some antibiotics against bacteria involved in acne production.展开更多
Garcinia mangostana, commonly known as mangosteen, is a tropical fruit with a reddish-purple pericarp. In Southeast Asia, the pericarp has traditionally been used as a medicine to treat various diseases, including inf...Garcinia mangostana, commonly known as mangosteen, is a tropical fruit with a reddish-purple pericarp. In Southeast Asia, the pericarp has traditionally been used as a medicine to treat various diseases, including inflammation, wounds, and bacterial infections, as well as aging. α-mangostin is an abundant xanthone in the pericarp, and is thought to play a critical role in the medicinal effects of mangosteens. Previous studies have demonstrated numerous beneficial effects of α-mangostin, such as cytotoxicity in cancer cells. However, the effects of this xanthone in in vivo have not yet been studied. In the current study, C. elegans was used to test the in vivo effects of α-mangostin using several bioassays, including fat accumulation, pharyngeal movement (pumping) and heat-stress assays. Quantitative real time PCR (qRT-PCR) was also used to examine the expression of heat shock proteins. The results revealed that α-mangostin appeared to cause an increase in fat accumulation, which correlated with an increase in pharyngeal movement. The thrashing movement of the worms after heat stress also showed a correlation with an increase in heat shock protein mRNA expression.展开更多
Objective:To test direct and indirect antimicrobial properties of α-mangostin towards a number of bacteria and fungi.Methods:Activity of α-mangostin paired with an antibiotic was studied by calculating its fractiona...Objective:To test direct and indirect antimicrobial properties of α-mangostin towards a number of bacteria and fungi.Methods:Activity of α-mangostin paired with an antibiotic was studied by calculating its fractional inhibitory concentration(FIC).Results:The experiment was carried out using broth microdilution and checkerboards methods.tetracycline showed no interaction with the combination withα-mangostin where the FIC indexes were between the range of 0.5<FIC_(index)>4.Activity of doxycycline on Pseudomonas aeruginosa fell into other set of range,FIC_(index)≥4 which is an antagonism.The activity of all four bacteria towards ampicillin,penicillin G,streptomycin and Conclusions:The FIC index is far away in the range.The coupled antibiotic andα-mangostin is considered synergy in action if it lies in FIC_(index)≤0.5 and it was found that the isolated compound,α-mangostin revealed very low synergistic antimicrobial effects when coupled with antibiotics.展开更多
选取传统中药提取单体化合物α-倒捻子素和8-甲氧基补骨脂素,通过2种药物敏感性实验方法MABA(Microdilution Alamar Blue Assay)分析与试管法分别测定了两种化合物对结核分枝杆菌H37Rv(ATCC27294)和H37Ra(ATCC25177)的体外抗菌活性,同...选取传统中药提取单体化合物α-倒捻子素和8-甲氧基补骨脂素,通过2种药物敏感性实验方法MABA(Microdilution Alamar Blue Assay)分析与试管法分别测定了两种化合物对结核分枝杆菌H37Rv(ATCC27294)和H37Ra(ATCC25177)的体外抗菌活性,同时还测定了9种阳性抗结核药物对这两种结核菌的最低抑菌浓度(MIC),比较2种方法的检测结果。结果表明:α-倒捻子素对结核分枝杆菌H37Rv(ATCC27294)和H37Ra(ATCC25177)的最低抑菌浓度均为6.25μg/mL,而8-甲氧基补骨脂素对结核分枝杆菌H37Rv(ATCC27294)和H37Ra(ATCC25177)的最低抑菌浓度均为128μg/mL。Alamar B1ue法与试管法相比较,完全符合率是90%(9/11),具有较好的一致性。本研究结果表明Mamar B1ue法是一种快速、简便测定药物对结核分枝杆菌MIC的方法。本研究为α-倒捻子素和8-甲氧基补骨脂素的进一步开发利用和抗分枝杆菌机制研究打下了基础。展开更多
基金Supported by The Thailand Research Fund,Grant No. RMU 4980043
文摘AIM:To investigate the effect of α-mangostin on the growth and apoptosis induction of human colon cancer cells.METHODS:The three colorectal adenocarcinoma cell lines tested (COLO 205,MIP-101 and SW 620) were treated with α-mangostin to determine the effect on cell proliferation by MTT assay,cell morphology,chromatin condensation,cell cycle analysis,DNA fragmentation,phosphatidylserine exposure and changing of mitochondrial membrane potential.The molecular mechanisms of α-mangostin mediated apoptosis were further investigated by Western blotting analysis including activation of caspase cascade,cytochrome c release,Bax,Bid,p53 and Bcl-2 modifying factor.RESULTS:The highest inhibitory effect of α-mangostin on cell proliferation of COLO 205,MIP-101 and SW 620 were 9.74 ± 0.85 μg/mL,11.35 ± 1.12 μg/mL and 19.6 ± 1.53 μg/mL,respectively.Further study showed that α-mangostin induced apoptotic cell death in COLO 205 cells as indicated by membrane blebbing,chromatin condensation,DNA fragmentation,cell cycle analysis,sub-G1 peak (P < 0.05) and phosphatidylserine exposure.The executioner caspase,caspase-3,the initiator caspase,caspase-8,and caspase-9 were expressed upon treatment with α-mangostin.Further studies of apoptotic proteins were determined by Western blotting analysis showing increased mitochondrial cytochrome c release,Bax,p53 and Bmf as well as reduced mitochondrial membrane potential (P < 0.05).In addition,up-regulation of tBid and Fas were evident upon treatment with α-mangostin (P < 0.01).CONCLUSION:α-Mangostin may be effective as an anti-cancer agent that induced apoptotic cell death in COLO 205 via a link between extrinsic and intrinsic pathways.
基金financially supported by Chulalongkorn Universitythe Doctoral Degree Chulalongkorn University 100th Year Birthday Anniversary+1 种基金the 90th Anniversary of Chulalongkorn University Fund(Ratchadaphiseksomphot Endowment Fund)Sci-Super IV_61_003 and the Overseas Research Experience Scholarship for Graduate Student
文摘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: 毩-Mangostin and apigenin were reported in comparison to doxorubicin, a chemotherapeutic drug. Ductal carcinoma(BT474) cell line and nontumorigenic epithelial tissue from mammary gland(MCF-10 A) 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 observed using propidium iodide st桋 and propidium iodide staining while cell-cycle arrest wasaining. 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 and apigenin were more cytotoxic to BT474 cells. Longer exposure times to 毩-mangostin enin caused more floating cells and a lower density of adhered cells wi毩-mangostin and apigth more vacuoles present in the colonies in BT474 only. 毩-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, 毩-mangostin and apigenin arrested the cellcycle 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, autophagyassociated and apoptosis-associated genes. Conclusions: ntial new sources of chemotherapeuti毩-Mangostin and apigenin are worth investigating as potec agents for breast cancer treatment.
基金Supported by the TWAS research grant 14-062 RG/BIO/AS_GNAFOSTED grant 106-NN.02–2016.19National Research Council of Thailand(NRCT)and Center of Excellence for Innovation in Chemistry(PERCH-CIC)
文摘Objective: To isolate a-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 methicillinsensitive 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 Bac Light stains. Biofilm composition was determined using specific chemical and enzyme tests for polysaccharide, protein and DNA. Membranedamaging 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 mmol/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 mmol/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.
基金the National Research Council of Thailand(NRCT)for providing a research grant.
文摘Objective:To evaluate the synergistic effect ofα-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)ofα-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 for24 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 6.25μg/m L,respectively.The results of the checkerboard assay showed thatα-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 thatα-mangostin increased the antibacterial activity of tetracycline,erythromycin,and clindamycin.Conclusion:These findings suggested thatα-mangostin may be used to enhance the antibacterial activity of some antibiotics against bacteria involved in acne production.
文摘Garcinia mangostana, commonly known as mangosteen, is a tropical fruit with a reddish-purple pericarp. In Southeast Asia, the pericarp has traditionally been used as a medicine to treat various diseases, including inflammation, wounds, and bacterial infections, as well as aging. α-mangostin is an abundant xanthone in the pericarp, and is thought to play a critical role in the medicinal effects of mangosteens. Previous studies have demonstrated numerous beneficial effects of α-mangostin, such as cytotoxicity in cancer cells. However, the effects of this xanthone in in vivo have not yet been studied. In the current study, C. elegans was used to test the in vivo effects of α-mangostin using several bioassays, including fat accumulation, pharyngeal movement (pumping) and heat-stress assays. Quantitative real time PCR (qRT-PCR) was also used to examine the expression of heat shock proteins. The results revealed that α-mangostin appeared to cause an increase in fat accumulation, which correlated with an increase in pharyngeal movement. The thrashing movement of the worms after heat stress also showed a correlation with an increase in heat shock protein mRNA expression.
基金Supported by the Research Management Centre(RMC)of IIUM(Grant No.EDWB11-018-04960)the e-science fund from the Ministry of Science,Technology and Innovation of Malaysia(Grant No.02-01-08-SF0110).
文摘Objective:To test direct and indirect antimicrobial properties of α-mangostin towards a number of bacteria and fungi.Methods:Activity of α-mangostin paired with an antibiotic was studied by calculating its fractional inhibitory concentration(FIC).Results:The experiment was carried out using broth microdilution and checkerboards methods.tetracycline showed no interaction with the combination withα-mangostin where the FIC indexes were between the range of 0.5<FIC_(index)>4.Activity of doxycycline on Pseudomonas aeruginosa fell into other set of range,FIC_(index)≥4 which is an antagonism.The activity of all four bacteria towards ampicillin,penicillin G,streptomycin and Conclusions:The FIC index is far away in the range.The coupled antibiotic andα-mangostin is considered synergy in action if it lies in FIC_(index)≤0.5 and it was found that the isolated compound,α-mangostin revealed very low synergistic antimicrobial effects when coupled with antibiotics.
