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Yuan Soon Ho - One of the best experts on this subject based on the ideXlab platform.
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study of the antitumor mechanisms of Apiole derivatives ap 02 from petroselinum crispum through induction of g0 g1 phase cell cycle arrest in human colo 205 cancer cells
BMC Complementary and Alternative Medicine, 2019Co-Authors: Kuan Hsun Wu, Hsiu Man Lien, Li Ching Chen, Hui Wen Chang, Yuan Soon Ho, Tzu Chun Cheng, Chia Chang ChenAbstract:Apiole was isolated from the leaves of various plants and vegetables and has been demonstrated to inhibit human colon cancer cell (COLO 205 cells) growth through induction of G0/G1 cell cycle arrest and apoptotic cell death. This study further explored the antitumor effects of Apiole derivatives AP-02, 04, and 05 in COLO 205 cancer cells. Human breast (MDA-MB-231, ZR75), lung (A549, PE089), colon (COLO 205, HT 29), and hepatocellular (Hep G2, Hep 3B) cancer cells were treated with Apiole and its derivatives in a dose-dependent manner. Flow cytometry analysis was subsequently performed to determine the mechanism of AP-02-induced G0/G1 cell cycle arrest. The in vivo antitumor effect of AP-02 (1 and 5 mg/kg, administered twice per week) was examined by treating athymic nude mice bearing COLO 205 tumor xenografts. The molecular mechanisms of AP-02-induced antitumor effects were determined using western blot analysis. AP-02 was the most effective compound, especially for inhibition of COLO 205 colon cancer cell growth. The cytotoxicity of AP-02 in normal colon epithelial (FHC) cells was significantly lower than that in other normal cells derived from the breast, lung or liver. Flow cytometry analysis indicated that AP-02-induced G0/G1 cell cycle arrest in COLO 205 cells but not in HT 29 cells ( 1 mg/kg)-treated athymic nude mice bearing COLO 205 tumor xenografts compared to control mice (*p 1 mg/kg, *p < 0.05). Our results provide in vitro and in vivo molecular evidence of AP-02-induced anti-proliferative effects on colon cancer, indicating that this compound might have potential clinical applications.
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Study of the antitumor mechanisms of Apiole derivatives (AP-02) from Petroselinum crispum through induction of G0/G1 phase cell cycle arrest in human COLO 205 cancer cells
BMC Complementary and Alternative Medicine, 2019Co-Authors: Kuan Hsun Wu, Hsiu Man Lien, Li Ching Chen, Hui Wen Chang, Tzu Chun Cheng, Chia Chang Chen, Yuan Soon HoAbstract:Apiole was isolated from the leaves of various plants and vegetables and has been demonstrated to inhibit human colon cancer cell (COLO 205 cells) growth through induction of G0/G1 cell cycle arrest and apoptotic cell death. This study further explored the antitumor effects of Apiole derivatives AP-02, 04, and 05 in COLO 205 cancer cells. Human breast (MDA-MB-231, ZR75), lung (A549, PE089), colon (COLO 205, HT 29), and hepatocellular (Hep G2, Hep 3B) cancer cells were treated with Apiole and its derivatives in a dose-dependent manner. Flow cytometry analysis was subsequently performed to determine the mechanism of AP-02-induced G0/G1 cell cycle arrest. The in vivo antitumor effect of AP-02 (1 and 5 mg/kg, administered twice per week) was examined by treating athymic nude mice bearing COLO 205 tumor xenografts. The molecular mechanisms of AP-02-induced antitumor effects were determined using western blot analysis. AP-02 was the most effective compound, especially for inhibition of COLO 205 colon cancer cell growth. The cytotoxicity of AP-02 in normal colon epithelial (FHC) cells was significantly lower than that in other normal cells derived from the breast, lung or liver. Flow cytometry analysis indicated that AP-02-induced G0/G1 cell cycle arrest in COLO 205 cells but not in HT 29 cells ( 1 mg/kg)-treated athymic nude mice bearing COLO 205 tumor xenografts compared to control mice (*p 1 mg/kg, *p
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the in vivo antitumor effects on human colo 205 cancer cells of the 4 7 dimethoxy 5 2 propen 1 yl 1 3 benzodioxole Apiole derivative of 5 substituted 4 7 dimethoxy 5 methyl l 3 benzodioxole sy 1 isolated from the fruiting body of antrodia camphorate
Journal of Cancer Research and Therapeutics, 2012Co-Authors: Shih Hsin Tu, Hsiu Man Lien, Li Ching Chen, Ching Shyang Chen, Chih Hsiung Wu, Ching Shui Huang, Hui Wen Chang, Chien Hsi Chang, How Tseng, Yuan Soon HoAbstract:CONTEXT: The compound 4,7-dimethoxy-5-(2-propen-1-yl)-1,3-benzodioxole (Apiole) has been isolated from several different plant species, including Petroselinum sativum. Our recent study found that Apiole is a chemical derivative of 4,7-dimethoxy-5-methyl-l,3-benzodioxole (SY-1), which has been isolated from dried Antrodia camphorata (AC ) fruiting bodies, a traditional Chinese medicine with antitumor properties. AIMS: Our previous in vitro study demonstrated that Apiole inhibits the growth of human colon (COLO 205) cancer cells through the arrest of the cell cycle in G0/G1 phase. The in vivo antitumor effects of Apiole were evaluated in this study. SETTING AND DESIGN: Apiole was administered to mice at 1-30 mg/kg body weight through intraperitoneal (I.P.) injection three times per week (defined as a dosage of 1×-30×). MATERIALS AND METHODS: The in vivo antitumor effects of Apiole were evaluated in mice with xenografts of COLO 205 cells. STATISTICAL ANALYSIS: All of the data are reported as the means ± S.E. Comparisons were performed with a one-way analysis of variance (ANOVA) followed by a Fisher's least significant difference test. Significance was defined as P 1×) markedly decreased the growth of COLO 205 human colon cancer cell tumor xenografts in an athymic nude mouse model system through the up-regulation of cell cycle regulators, such as p53, p21/Cip1, and p27/Kip1. The Apiole-induced increase in G0/G1 phase cell cycle regulators was also associated with a significant decrease in the expression of cyclins D1 and D3. Surprisingly, statistically significantly higher tumor volumes were observed in mice that received 5× Apiole compared with 30× Apiole-treated mice (P < 0.05). No gross signs of toxicity were observed (e.g., body weight changes, general appearance, or individual organ effects) in any group. CONCLUSIONS: Our results show, for the first time, the promising antitumor effects of Apiole against colon tumors in an in vivo xenograft model.
Li Ching Chen - One of the best experts on this subject based on the ideXlab platform.
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study of the antitumor mechanisms of Apiole derivatives ap 02 from petroselinum crispum through induction of g0 g1 phase cell cycle arrest in human colo 205 cancer cells
BMC Complementary and Alternative Medicine, 2019Co-Authors: Kuan Hsun Wu, Hsiu Man Lien, Li Ching Chen, Hui Wen Chang, Yuan Soon Ho, Tzu Chun Cheng, Chia Chang ChenAbstract:Apiole was isolated from the leaves of various plants and vegetables and has been demonstrated to inhibit human colon cancer cell (COLO 205 cells) growth through induction of G0/G1 cell cycle arrest and apoptotic cell death. This study further explored the antitumor effects of Apiole derivatives AP-02, 04, and 05 in COLO 205 cancer cells. Human breast (MDA-MB-231, ZR75), lung (A549, PE089), colon (COLO 205, HT 29), and hepatocellular (Hep G2, Hep 3B) cancer cells were treated with Apiole and its derivatives in a dose-dependent manner. Flow cytometry analysis was subsequently performed to determine the mechanism of AP-02-induced G0/G1 cell cycle arrest. The in vivo antitumor effect of AP-02 (1 and 5 mg/kg, administered twice per week) was examined by treating athymic nude mice bearing COLO 205 tumor xenografts. The molecular mechanisms of AP-02-induced antitumor effects were determined using western blot analysis. AP-02 was the most effective compound, especially for inhibition of COLO 205 colon cancer cell growth. The cytotoxicity of AP-02 in normal colon epithelial (FHC) cells was significantly lower than that in other normal cells derived from the breast, lung or liver. Flow cytometry analysis indicated that AP-02-induced G0/G1 cell cycle arrest in COLO 205 cells but not in HT 29 cells ( 1 mg/kg)-treated athymic nude mice bearing COLO 205 tumor xenografts compared to control mice (*p 1 mg/kg, *p < 0.05). Our results provide in vitro and in vivo molecular evidence of AP-02-induced anti-proliferative effects on colon cancer, indicating that this compound might have potential clinical applications.
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Study of the antitumor mechanisms of Apiole derivatives (AP-02) from Petroselinum crispum through induction of G0/G1 phase cell cycle arrest in human COLO 205 cancer cells
BMC Complementary and Alternative Medicine, 2019Co-Authors: Kuan Hsun Wu, Hsiu Man Lien, Li Ching Chen, Hui Wen Chang, Tzu Chun Cheng, Chia Chang Chen, Yuan Soon HoAbstract:Apiole was isolated from the leaves of various plants and vegetables and has been demonstrated to inhibit human colon cancer cell (COLO 205 cells) growth through induction of G0/G1 cell cycle arrest and apoptotic cell death. This study further explored the antitumor effects of Apiole derivatives AP-02, 04, and 05 in COLO 205 cancer cells. Human breast (MDA-MB-231, ZR75), lung (A549, PE089), colon (COLO 205, HT 29), and hepatocellular (Hep G2, Hep 3B) cancer cells were treated with Apiole and its derivatives in a dose-dependent manner. Flow cytometry analysis was subsequently performed to determine the mechanism of AP-02-induced G0/G1 cell cycle arrest. The in vivo antitumor effect of AP-02 (1 and 5 mg/kg, administered twice per week) was examined by treating athymic nude mice bearing COLO 205 tumor xenografts. The molecular mechanisms of AP-02-induced antitumor effects were determined using western blot analysis. AP-02 was the most effective compound, especially for inhibition of COLO 205 colon cancer cell growth. The cytotoxicity of AP-02 in normal colon epithelial (FHC) cells was significantly lower than that in other normal cells derived from the breast, lung or liver. Flow cytometry analysis indicated that AP-02-induced G0/G1 cell cycle arrest in COLO 205 cells but not in HT 29 cells ( 1 mg/kg)-treated athymic nude mice bearing COLO 205 tumor xenografts compared to control mice (*p 1 mg/kg, *p
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the in vivo antitumor effects on human colo 205 cancer cells of the 4 7 dimethoxy 5 2 propen 1 yl 1 3 benzodioxole Apiole derivative of 5 substituted 4 7 dimethoxy 5 methyl l 3 benzodioxole sy 1 isolated from the fruiting body of antrodia camphorate
Journal of Cancer Research and Therapeutics, 2012Co-Authors: Shih Hsin Tu, Hsiu Man Lien, Li Ching Chen, Ching Shyang Chen, Chih Hsiung Wu, Ching Shui Huang, Hui Wen Chang, Chien Hsi Chang, How Tseng, Yuan Soon HoAbstract:CONTEXT: The compound 4,7-dimethoxy-5-(2-propen-1-yl)-1,3-benzodioxole (Apiole) has been isolated from several different plant species, including Petroselinum sativum. Our recent study found that Apiole is a chemical derivative of 4,7-dimethoxy-5-methyl-l,3-benzodioxole (SY-1), which has been isolated from dried Antrodia camphorata (AC ) fruiting bodies, a traditional Chinese medicine with antitumor properties. AIMS: Our previous in vitro study demonstrated that Apiole inhibits the growth of human colon (COLO 205) cancer cells through the arrest of the cell cycle in G0/G1 phase. The in vivo antitumor effects of Apiole were evaluated in this study. SETTING AND DESIGN: Apiole was administered to mice at 1-30 mg/kg body weight through intraperitoneal (I.P.) injection three times per week (defined as a dosage of 1×-30×). MATERIALS AND METHODS: The in vivo antitumor effects of Apiole were evaluated in mice with xenografts of COLO 205 cells. STATISTICAL ANALYSIS: All of the data are reported as the means ± S.E. Comparisons were performed with a one-way analysis of variance (ANOVA) followed by a Fisher's least significant difference test. Significance was defined as P 1×) markedly decreased the growth of COLO 205 human colon cancer cell tumor xenografts in an athymic nude mouse model system through the up-regulation of cell cycle regulators, such as p53, p21/Cip1, and p27/Kip1. The Apiole-induced increase in G0/G1 phase cell cycle regulators was also associated with a significant decrease in the expression of cyclins D1 and D3. Surprisingly, statistically significantly higher tumor volumes were observed in mice that received 5× Apiole compared with 30× Apiole-treated mice (P < 0.05). No gross signs of toxicity were observed (e.g., body weight changes, general appearance, or individual organ effects) in any group. CONCLUSIONS: Our results show, for the first time, the promising antitumor effects of Apiole against colon tumors in an in vivo xenograft model.
Maor Barpeled - One of the best experts on this subject based on the ideXlab platform.
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synthesis of udp apiose in bacteria the marine phototroph geminicoccus roseus and the plant pathogen xanthomonas pisi
PLOS ONE, 2017Co-Authors: James Amor Smith, Maor BarpeledAbstract:: The branched-chain sugar apiose was widely assumed to be synthesized only by plant species. In plants, apiose-containing polysaccharides are found in vascularized plant cell walls as the pectic polymers rhamnogalacturonan II and apiogalacturonan. Apiosylated secondary metabolites are also common in many plant species including ancestral avascular bryophytes and green algae. Apiosyl-residues have not been documented in bacteria. In a screen for new bacterial glycan structures, we detected small amounts of apiose in methanolic extracts of the aerobic phototroph Geminicoccus roseus and the pathogenic soil-dwelling bacteria Xanthomonas pisi. Apiose was also present in the cell pellet of X. pisi. Examination of these bacterial genomes uncovered genes with relatively low protein homology to plant UDP-apiose/UDP-xylose synthase (UAS). Phylogenetic analysis revealed that these bacterial UAS-like homologs belong in a clade distinct to UAS and separated from other nucleotide sugar biosynthetic enzymes. Recombinant expression of three bacterial UAS-like proteins demonstrates that they actively convert UDP-glucuronic acid to UDP-apiose and UDP-xylose. Both UDP-apiose and UDP-xylose were detectable in cell cultures of G. roseus and X. pisi. We could not, however, definitively identify the apiosides made by these bacteria, but the detection of apiosides coupled with the in vivo transcription of bUAS and production of UDP-apiose clearly demonstrate that these microbes have evolved the ability to incorporate apiose into glycans during their lifecycles. While this is the first report to describe enzymes for the formation of activated apiose in bacteria, the advantage of synthesizing apiose-containing glycans in bacteria remains unknown. The characteristics of bUAS and its products are discussed.
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functional characterization of udp apiose synthases from bryophytes and green algae provides insight into the appearance of apiose containing glycans during plant evolution
Journal of Biological Chemistry, 2016Co-Authors: J C Smith, Yiwen Yang, Shahar Levy, Oluwatoyin Oluwayemi Adelusi, Michael G Hahn, Malcolm A Oneill, Maor BarpeledAbstract:Abstract Apiose is a branched monosaccharide that is present in the cell wall pectic polysaccharides rhamnogalacturonan II and apiogalacturonan and in numerous plant secondary metabolites. These apiose-containing glycans are synthesized using UDP-apiose as the donor. UDP-apiose (UDP-Api) together with UDP-xylose is formed from UDP-glucuronic acid (UDP-GlcA) by UDP-Api synthase (UAS). It was hypothesized that the ability to form Api distinguishes vascular plants from the avascular plants and green algae. UAS from several dicotyledonous plants has been characterized; however, it is not known if avascular plants or green algae produce this enzyme. Here we report the identification and functional characterization of UAS homologs from avascular plants (mosses, liverwort, and hornwort), from streptophyte green algae, and from a monocot (duckweed). The recombinant UAS homologs all form UDP-Api from UDP-glucuronic acid albeit in different amounts. Apiose was detected in aqueous methanolic extracts of these plants. Apiose was detected in duckweed cell walls but not in the walls of the avascular plants and algae. Overexpressing duckweed UAS in the moss Physcomitrella patens led to an increase in the amounts of aqueous methanol-acetonitrile-soluble apiose but did not result in discernible amounts of cell wall-associated apiose. Thus, bryophytes and algae likely lack the glycosyltransferase machinery required to synthesize apiose-containing cell wall glycans. Nevertheless, these plants may have the ability to form apiosylated secondary metabolites. Our data are the first to provide evidence that the ability to form apiose existed prior to the appearance of rhamnogalacturonan II and apiogalacturonan and provide new insights into the evolution of apiose-containing glycans.
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real time nmr monitoring of intermediates and labile products of the bifunctional enzyme udp apiose udp xylose synthase
Carbohydrate Research, 2009Co-Authors: Paul J Guyett, John Glushka, Xiaogang Gu, Maor BarpeledAbstract:Abstract The conversion of UDP-α- d -glucuronic acid to UDP-α- d -xylose and UDP-α- d -apiose by a bifunctional potato enzyme UDP-apiose/UDP-xylose synthase was studied using real-time nuclear magnetic resonance (NMR) spectroscopy. UDP-α- d -glucuronic acid is converted via the intermediate uridine 5′-β- l -threo-pentapyranosyl-4″-ulose diphosphate to UDP-α- d -apiose and simultaneously to UDP-α- d -xylose. The UDP-α- d -apiose that is formed is unstable and is converted to α- d -apio-furanosyl-1,2-cyclic phosphate and UMP. High-resolution real-time NMR spectroscopy is a powerful tool for the direct and quantitative characterization of previously undetected transient and labile components formed during a complex enzyme-catalyzed reaction.
Wolfdieter Reiter - One of the best experts on this subject based on the ideXlab platform.
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depletion of udp d apiose udp d xylose synthases results in rhamnogalacturonan ii deficiency cell wall thickening and cell death in higher plants
Journal of Biological Chemistry, 2006Co-Authors: Rajeev Verma, Jae Wook Bang, Wolfdieter ReiterAbstract:Abstract d-Apiose serves as the binding site for borate cross-linking of rhamnogalacturonan II (RG-II) in the plant cell wall, and biosynthesis of d-apiose involves UDP-d-apiose/UDP-d-xylose synthase catalyzing the conversion of UDP-d-glucuronate to a mixture of UDP-d-apiose and UDP-d-xylose. In this study we have analyzed the cellular effects of depletion of UDP-d-apiose/UDP-d-xylose synthases in plants by using virus-induced gene silencing (VIGS) of NbAXS1 in Nicotiana benthamiana. The recombinant NbAXS1 protein exhibited UDP-d-apiose/UDP-d-xylose synthase activity in vitro. The NbAXS1 gene was expressed in all major plant organs, and an NbAXS1-green fluorescent protein fusion protein was mostly localized in the cytosol. VIGS of NbAXS1 resulted in growth arrest and leaf yellowing. Microscopic studies of the leaf cells of the NbAXS1 VIGS lines revealed cell death symptoms including cell lysis and disintegration of cellular organelles and compartments. The cell death was accompanied by excessive formation of reactive oxygen species and by induction of various protease genes. Furthermore, abnormal wall structure of the affected cells was evident including excessive cell wall thickening and wall gaps. The mutant cell walls contained significantly reduced levels of d-apiose as well as 2-O-methyl-l-fucose and 2-O-methyl-d-xylose, which serve as markers for the RG-II side chains B and A, respectively. These results suggest that VIGS of NbAXS1 caused a severe deficiency in the major side chains of RG-II and that the growth defect and cell death was likely caused by structural alterations in RG-II due to a d-apiose deficiency.
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Depletion of UDP-D-apiose/UDP-D-xylose synthases results in rhamnogalacturonan-II deficiency, cell wall thickening, and cell death in higher plants
Journal of Biological Chemistry, 2006Co-Authors: Rajeev Verma, Jae Wook Bang, Wolfdieter ReiterAbstract:Abstract d-Apiose serves as the binding site for borate cross-linking of rhamnogalacturonan II (RG-II) in the plant cell wall, and biosynthesis of d-apiose involves UDP-d-apiose/UDP-d-xylose synthase catalyzing the conversion of UDP-d-glucuronate to a mixture of UDP-d-apiose and UDP-d-xylose. In this study we have analyzed the cellular effects of depletion of UDP-d-apiose/UDP-d-xylose synthases in plants by using virus-induced gene silencing (VIGS) of NbAXS1 in Nicotiana benthamiana. The recombinant NbAXS1 protein exhibited UDP-d-apiose/UDP-d-xylose synthase activity in vitro. The NbAXS1 gene was expressed in all major plant organs, and an NbAXS1-green fluorescent protein fusion protein was mostly localized in the cytosol. VIGS of NbAXS1 resulted in growth arrest and leaf yellowing. Microscopic studies of the leaf cells of the NbAXS1 VIGS lines revealed cell death symptoms including cell lysis and disintegration of cellular organelles and compartments. The cell death was accompanied by excessive formation of reactive oxygen species and by induction of various protease genes. Furthermore, abnormal wall structure of the affected cells was evident including excessive cell wall thickening and wall gaps. The mutant cell walls contained significantly reduced levels of d-apiose as well as 2-O-methyl-l-fucose and 2-O-methyl-d-xylose, which serve as markers for the RG-II side chains B and A, respectively. These results suggest that VIGS of NbAXS1 caused a severe deficiency in the major side chains of RG-II and that the growth defect and cell death was likely caused by structural alterations in RG-II due to a d-apiose deficiency.
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the biosynthesis of the branched chain sugar d apiose in plants functional cloning and characterization of a udp d apiose udp d xylose synthase from arabidopsis
Plant Journal, 2003Co-Authors: Michael Molhoj, Rajeev Verma, Wolfdieter ReiterAbstract:Summary d-Apiose is a plant-specific branched-chain monosaccharide found in rhamnogalacturonan II (RG-II), apiogalacturonan, and several apioglycosides. Within RG-II, d-apiose serves as the binding site for borate, which leads to the formation of cross-links within the wall. Biochemical studies in duckweed and parsley have established that uridine 5′-diphospho-d-apiose (UDP-d-apiose) is formed from UDP-d-glucuronate by decarboxylation and re-arrangement of the carbon skeleton, leading to ring contraction and branch formation. The enzyme catalyzing this reaction also forms UDP-d-xylose by decarboxylation of UDP-d-glucuronate, and has therefore been named UDP-d-apiose/UDP-d-xylose synthase. Using a bioinformatics approach, we identified a candidate gene (AXS1) for this enzyme in Arabidopsis and functionally expressed its cDNA in Escherichia coli. The recombinant enzyme catalyzed the conversion of UDP-d-glucuronate to a mixture of UDP-d-apiose and UDP-d-xylose with a turnover number of 0.3 min-1. AXS1 required NAD+ for enzymatic activity, and was strongly inhibited by UDP-d-galacturonate. It was highly expressed in all plant organs consistent with a function in synthesizing an essential cell wall precursor. Database searches indicated the presence of closely related sequences in a variety of crop plants. The cloning of the AXS1 gene will help to investigate the biosynthesis of RG-II, and permit insights into the mechanism by which d-apiose and other branched monosaccharides are formed.
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The biosynthesis of the branched‐chain sugar d‐apiose in plants: functional cloning and characterization of a UDP‐d‐apiose/UDP‐d‐xylose synthase from Arabidopsis
Plant Journal, 2003Co-Authors: Michael Molhoj, Rajeev Verma, Wolfdieter ReiterAbstract:Summary d-Apiose is a plant-specific branched-chain monosaccharide found in rhamnogalacturonan II (RG-II), apiogalacturonan, and several apioglycosides. Within RG-II, d-apiose serves as the binding site for borate, which leads to the formation of cross-links within the wall. Biochemical studies in duckweed and parsley have established that uridine 5′-diphospho-d-apiose (UDP-d-apiose) is formed from UDP-d-glucuronate by decarboxylation and re-arrangement of the carbon skeleton, leading to ring contraction and branch formation. The enzyme catalyzing this reaction also forms UDP-d-xylose by decarboxylation of UDP-d-glucuronate, and has therefore been named UDP-d-apiose/UDP-d-xylose synthase. Using a bioinformatics approach, we identified a candidate gene (AXS1) for this enzyme in Arabidopsis and functionally expressed its cDNA in Escherichia coli. The recombinant enzyme catalyzed the conversion of UDP-d-glucuronate to a mixture of UDP-d-apiose and UDP-d-xylose with a turnover number of 0.3 min-1. AXS1 required NAD+ for enzymatic activity, and was strongly inhibited by UDP-d-galacturonate. It was highly expressed in all plant organs consistent with a function in synthesizing an essential cell wall precursor. Database searches indicated the presence of closely related sequences in a variety of crop plants. The cloning of the AXS1 gene will help to investigate the biosynthesis of RG-II, and permit insights into the mechanism by which d-apiose and other branched monosaccharides are formed.
Hsiu Man Lien - One of the best experts on this subject based on the ideXlab platform.
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Study of the antitumor mechanisms of Apiole derivatives (AP-02) from Petroselinum crispum through induction of G0/G1 phase cell cycle arrest in human COLO 205 cancer cells
BMC Complementary and Alternative Medicine, 2019Co-Authors: Kuan Hsun Wu, Hsiu Man Lien, Li Ching Chen, Hui Wen Chang, Tzu Chun Cheng, Chia Chang Chen, Yuan Soon HoAbstract:Apiole was isolated from the leaves of various plants and vegetables and has been demonstrated to inhibit human colon cancer cell (COLO 205 cells) growth through induction of G0/G1 cell cycle arrest and apoptotic cell death. This study further explored the antitumor effects of Apiole derivatives AP-02, 04, and 05 in COLO 205 cancer cells. Human breast (MDA-MB-231, ZR75), lung (A549, PE089), colon (COLO 205, HT 29), and hepatocellular (Hep G2, Hep 3B) cancer cells were treated with Apiole and its derivatives in a dose-dependent manner. Flow cytometry analysis was subsequently performed to determine the mechanism of AP-02-induced G0/G1 cell cycle arrest. The in vivo antitumor effect of AP-02 (1 and 5 mg/kg, administered twice per week) was examined by treating athymic nude mice bearing COLO 205 tumor xenografts. The molecular mechanisms of AP-02-induced antitumor effects were determined using western blot analysis. AP-02 was the most effective compound, especially for inhibition of COLO 205 colon cancer cell growth. The cytotoxicity of AP-02 in normal colon epithelial (FHC) cells was significantly lower than that in other normal cells derived from the breast, lung or liver. Flow cytometry analysis indicated that AP-02-induced G0/G1 cell cycle arrest in COLO 205 cells but not in HT 29 cells ( 1 mg/kg)-treated athymic nude mice bearing COLO 205 tumor xenografts compared to control mice (*p 1 mg/kg, *p
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study of the antitumor mechanisms of Apiole derivatives ap 02 from petroselinum crispum through induction of g0 g1 phase cell cycle arrest in human colo 205 cancer cells
BMC Complementary and Alternative Medicine, 2019Co-Authors: Kuan Hsun Wu, Hsiu Man Lien, Li Ching Chen, Hui Wen Chang, Yuan Soon Ho, Tzu Chun Cheng, Chia Chang ChenAbstract:Apiole was isolated from the leaves of various plants and vegetables and has been demonstrated to inhibit human colon cancer cell (COLO 205 cells) growth through induction of G0/G1 cell cycle arrest and apoptotic cell death. This study further explored the antitumor effects of Apiole derivatives AP-02, 04, and 05 in COLO 205 cancer cells. Human breast (MDA-MB-231, ZR75), lung (A549, PE089), colon (COLO 205, HT 29), and hepatocellular (Hep G2, Hep 3B) cancer cells were treated with Apiole and its derivatives in a dose-dependent manner. Flow cytometry analysis was subsequently performed to determine the mechanism of AP-02-induced G0/G1 cell cycle arrest. The in vivo antitumor effect of AP-02 (1 and 5 mg/kg, administered twice per week) was examined by treating athymic nude mice bearing COLO 205 tumor xenografts. The molecular mechanisms of AP-02-induced antitumor effects were determined using western blot analysis. AP-02 was the most effective compound, especially for inhibition of COLO 205 colon cancer cell growth. The cytotoxicity of AP-02 in normal colon epithelial (FHC) cells was significantly lower than that in other normal cells derived from the breast, lung or liver. Flow cytometry analysis indicated that AP-02-induced G0/G1 cell cycle arrest in COLO 205 cells but not in HT 29 cells ( 1 mg/kg)-treated athymic nude mice bearing COLO 205 tumor xenografts compared to control mice (*p 1 mg/kg, *p < 0.05). Our results provide in vitro and in vivo molecular evidence of AP-02-induced anti-proliferative effects on colon cancer, indicating that this compound might have potential clinical applications.
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the in vivo antitumor effects on human colo 205 cancer cells of the 4 7 dimethoxy 5 2 propen 1 yl 1 3 benzodioxole Apiole derivative of 5 substituted 4 7 dimethoxy 5 methyl l 3 benzodioxole sy 1 isolated from the fruiting body of antrodia camphorate
Journal of Cancer Research and Therapeutics, 2012Co-Authors: Shih Hsin Tu, Hsiu Man Lien, Li Ching Chen, Ching Shyang Chen, Chih Hsiung Wu, Ching Shui Huang, Hui Wen Chang, Chien Hsi Chang, How Tseng, Yuan Soon HoAbstract:CONTEXT: The compound 4,7-dimethoxy-5-(2-propen-1-yl)-1,3-benzodioxole (Apiole) has been isolated from several different plant species, including Petroselinum sativum. Our recent study found that Apiole is a chemical derivative of 4,7-dimethoxy-5-methyl-l,3-benzodioxole (SY-1), which has been isolated from dried Antrodia camphorata (AC ) fruiting bodies, a traditional Chinese medicine with antitumor properties. AIMS: Our previous in vitro study demonstrated that Apiole inhibits the growth of human colon (COLO 205) cancer cells through the arrest of the cell cycle in G0/G1 phase. The in vivo antitumor effects of Apiole were evaluated in this study. SETTING AND DESIGN: Apiole was administered to mice at 1-30 mg/kg body weight through intraperitoneal (I.P.) injection three times per week (defined as a dosage of 1×-30×). MATERIALS AND METHODS: The in vivo antitumor effects of Apiole were evaluated in mice with xenografts of COLO 205 cells. STATISTICAL ANALYSIS: All of the data are reported as the means ± S.E. Comparisons were performed with a one-way analysis of variance (ANOVA) followed by a Fisher's least significant difference test. Significance was defined as P 1×) markedly decreased the growth of COLO 205 human colon cancer cell tumor xenografts in an athymic nude mouse model system through the up-regulation of cell cycle regulators, such as p53, p21/Cip1, and p27/Kip1. The Apiole-induced increase in G0/G1 phase cell cycle regulators was also associated with a significant decrease in the expression of cyclins D1 and D3. Surprisingly, statistically significantly higher tumor volumes were observed in mice that received 5× Apiole compared with 30× Apiole-treated mice (P < 0.05). No gross signs of toxicity were observed (e.g., body weight changes, general appearance, or individual organ effects) in any group. CONCLUSIONS: Our results show, for the first time, the promising antitumor effects of Apiole against colon tumors in an in vivo xenograft model.
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Study of the Anti-Proliferative Activity of 5-Substituted 4,7-Dimethoxy-1,3-Benzodioxole Derivatives of SY-1 from Antrodia camphorata on Human COLO 205 Colon Cancer Cells.
Evidence-based Complementary and Alternative Medicine, 2011Co-Authors: Hsiu Man Lien, Chao-lu Huang, Ding-yah YangAbstract:A set of 10 4,7-dimethoxy-1,3-benzodioxole derivatives based on a lead compound previously discovered by our group, SY-1, which was isolated from Antrodia camphorata, were evaluated for their in vitro inhibitory activity on human colorectal carcinoma cells (COLO 205). Structure-activity relationship studies of the 10 compounds indicated the importance of the chain length of the alkyl group at the 5-position, and the 2-propenyl substituent named “Apiole” exhibited the most potent inhibitory activity. In the present study, we demonstrate that the SY-1 analogue “Apiole” decreased the proliferation of COLO 205 cells, but not that of normal human colonic epithelial cells (FHC). The G0/G1 cell cycle arrest induced by Apiole (75–225 μM) was associated with significantly increased levels of p53, p21 and p27 and decreased levels of cyclin D1. Concerning COLO 205 cell apoptosis, Apiole (>150 μM) treatment significantly increased the levels of cleaved caspases 3, 8, 9 and bax/bcl-2 ratio and induced ladder formation in DNA fragmentation assay and sub-G1 peak in flow cytometry analysis. These findings suggest that Apiole can suppress COLO 205 cell growth; however, the detailed mechanisms of these processes require further investigation.
