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Title: Antitumor effects of the partially purified polysaccharides from Antrodia camphorata and the mechanism of its action

Abstract

Antrodia camphorata is a popular folk medicine that has attracted great attention due to its fame for antitumor activity against cancer. However, there is little information available about its action. In the present study, we purified a unique polysaccharide component from A. camphorata mycelia (AC-PS) and found that it has pronounced anti-tumor effects on both in vitro and in vivo model. Our results showed that AC-PS alone did not show any direct cytotoxic effect to human leukemic U937 cells, even at high concentration (200 {mu}g/ml). However, it could inhibit the proliferation of U937 cells via activation of mononuclear cells (MNCs). Treatment of U937 cells with AC-PS-stimulated-MNC-CM could significantly inhibit its proliferation with 55.3% growth inhibition rate. The in vitro antitumor activity was substantiated by the in vivo therapeutical study of AC-PS in sarcoma 180-bearing mice. Intraperitoneal and oral administration of AC-PS, 100 and 200 mg/kg significantly suppressed the tumor growth with the inhibition rate of 69.1% and 58.8%, respectively. In vivo studies also showed that several immunoparameters, such as the spontaneous proliferation of spleen cells, after AC-PS administration, were two-fold higher than in control mice. Furthermore, the cytolytic activity of spleen cells also increased from 9.8 {+-} 1.1% in controlmore » mice to 34.2 {+-} 5.5% and 48.2 {+-} 2.5%, after oral and intraperitoneal treatment, respectively. Besides, the mice serum interleukin-12 levels increased significantly by AC-PS treatment. Considering all these results, it is suggested that AC-PS elicit its anti-tumor effect by promoting a Th1-dominant state and killer activities.« less

Authors:
 [1];  [2];  [3];  [4];  [4];  [5];  [6]
  1. Graduate Institute of Biochemistry and Molecular Biology, College of Medicine, National Taiwan University, Taipei, Taiwan (China)
  2. Department of Internal Medicine, College of Medicine, National Taiwan University and National Taiwan University Hospital, Taipei, Taiwan (China)
  3. Department of Radiation Oncology, Mackay Memorial Hospital, Taipei, Taiwan (China)
  4. Biotechnology Center, Grape King Inc., Chungli, Taiwan (China)
  5. School of Applied Chemistry, Chung Shan Medical University, Taichung, Taiwan (China). E-mail: fjlu@csmu.edu.tw
  6. School of Applied Chemistry, Chung Shan Medical University, Taichung, Taiwan (China). E-mail: whchang@csmu.edu.tw
Publication Date:
OSTI Identifier:
20634826
Resource Type:
Journal Article
Resource Relation:
Journal Name: Toxicology and Applied Pharmacology; Journal Volume: 201; Journal Issue: 2; Other Information: DOI: 10.1016/j.taap.2004.05.016; PII: S0041-008X(04)00278-9; Copyright (c) 2004 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved; Country of input: International Atomic Energy Agency (IAEA)
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; BLOOD; CELL PROLIFERATION; DRUGS; IN VITRO; IN VIVO; MICE; ORAL ADMINISTRATION; POLYSACCHARIDES; SARCOMAS; SPLEEN CELLS

Citation Formats

Liu, J.-J., Huang, T.-S., Hsu, M.-L., Chen, C.-C., Lin, W.-S., Lu, F.-J., and Chang, W.-H. Antitumor effects of the partially purified polysaccharides from Antrodia camphorata and the mechanism of its action. United States: N. p., 2004. Web. doi:10.1016/j.taap.2004.05.016.
Liu, J.-J., Huang, T.-S., Hsu, M.-L., Chen, C.-C., Lin, W.-S., Lu, F.-J., & Chang, W.-H. Antitumor effects of the partially purified polysaccharides from Antrodia camphorata and the mechanism of its action. United States. doi:10.1016/j.taap.2004.05.016.
Liu, J.-J., Huang, T.-S., Hsu, M.-L., Chen, C.-C., Lin, W.-S., Lu, F.-J., and Chang, W.-H. Wed . "Antitumor effects of the partially purified polysaccharides from Antrodia camphorata and the mechanism of its action". United States. doi:10.1016/j.taap.2004.05.016.
@article{osti_20634826,
title = {Antitumor effects of the partially purified polysaccharides from Antrodia camphorata and the mechanism of its action},
author = {Liu, J.-J. and Huang, T.-S. and Hsu, M.-L. and Chen, C.-C. and Lin, W.-S. and Lu, F.-J. and Chang, W.-H.},
abstractNote = {Antrodia camphorata is a popular folk medicine that has attracted great attention due to its fame for antitumor activity against cancer. However, there is little information available about its action. In the present study, we purified a unique polysaccharide component from A. camphorata mycelia (AC-PS) and found that it has pronounced anti-tumor effects on both in vitro and in vivo model. Our results showed that AC-PS alone did not show any direct cytotoxic effect to human leukemic U937 cells, even at high concentration (200 {mu}g/ml). However, it could inhibit the proliferation of U937 cells via activation of mononuclear cells (MNCs). Treatment of U937 cells with AC-PS-stimulated-MNC-CM could significantly inhibit its proliferation with 55.3% growth inhibition rate. The in vitro antitumor activity was substantiated by the in vivo therapeutical study of AC-PS in sarcoma 180-bearing mice. Intraperitoneal and oral administration of AC-PS, 100 and 200 mg/kg significantly suppressed the tumor growth with the inhibition rate of 69.1% and 58.8%, respectively. In vivo studies also showed that several immunoparameters, such as the spontaneous proliferation of spleen cells, after AC-PS administration, were two-fold higher than in control mice. Furthermore, the cytolytic activity of spleen cells also increased from 9.8 {+-} 1.1% in control mice to 34.2 {+-} 5.5% and 48.2 {+-} 2.5%, after oral and intraperitoneal treatment, respectively. Besides, the mice serum interleukin-12 levels increased significantly by AC-PS treatment. Considering all these results, it is suggested that AC-PS elicit its anti-tumor effect by promoting a Th1-dominant state and killer activities.},
doi = {10.1016/j.taap.2004.05.016},
journal = {Toxicology and Applied Pharmacology},
number = 2,
volume = 201,
place = {United States},
year = {Wed Dec 01 00:00:00 EST 2004},
month = {Wed Dec 01 00:00:00 EST 2004}
}
  • Strains 6, 15, 98, 110, and 145 of Cryptococcus neoformans serotype A vary in capsule size, animal virulence, and susceptibility to in vitro phagocytosis. The isolated capsular polysaccharides (CPSs) differ in monosaccharide composition ratios and molecular size, as determined by gel filtration. The purpose of this investigation was to characterize the binding of CPSs to capsule-free mutants of C. neoformans and to examine CPSs from these strains for differences in their ability to bind, to determine whether such differences might explain the variation in the pathobiology of these strains. CPSs were partially periodate oxidized, tyraminated, iodinated with /sup 125/I, andmore » used in binding studies with two capsule-free mutants of C. neoformans, strain 602 and Cap59. Binding was specific for yeast species and for polysaccharide and was saturable, which is consistent with a receptor-mediated mechanism of attachment. Binding occurred rapidly and was only slowly reversible. Binding was also independent of pH from pH 5.5 to 8, of cation concentrations, and of competition by sugars up to 1.0 M concentrations. Only a portion of CPS was capable of binding, and strains varied in the extent to which their CPS bound. CPS-15-IV (peak IV was the major polysaccharide peak on DEAE-cellulose chromatography of CPS from strain 15) had the highest proportion of binding (40%), followed by CPS from strains 98, 6, 145, 110, and 15-III (peak III was an earlier eluting fraction of CPS from strain 15). The CPSs differed similarly in their ability to competitively inhibit binding. Treatment of CPS, but not yeast cells, with proteinase XIV abolished binding without altering the CPS gross structure. Treatment of yeast cells with proteases, heat, or formaldehyde did not alter binding, and both strain 602 and Cap59 bound CPS similarly. Binding to encapsulated yeast cells was minimal.« less
  • The ASCT2 transport system catalyses a sodium-dependent antiport of glutamine and other neutral amino acids which is involved in amino acid metabolism. A library of 1,2,3-dithiazoles was designed, synthesized and evaluated as inhibitors of the glutamine/amino acid ASCT2 transporter in the model system of proteoliposomes reconstituted with the rat liver transporter. Fifteen of the tested compounds at concentration of 20 μM or below, inhibited more than 50% the glutamine/glutamine antiport catalysed by the reconstituted transporter. These good inhibitors bear a phenyl ring with electron withdrawing substituents. The inhibition was reversed by 1,4-dithioerythritol indicating that the effect was likely owed tomore » the formation of mixed sulfides with the protein's Cys residue(s). A dose–response analysis of the most active compounds gave IC{sub 50} values in the range of 3–30 μM. Kinetic inhibition studies indicated a non-competitive inhibition, presumably because of a potential covalent interaction of the dithiazoles with cysteine thiol groups that are not located at the substrate binding site. Indeed, computational studies using a homology structural model of ASCT2 transporter, suggested as possible binding targets, Cys-207 or Cys-210, that belong to the CXXC motif of the protein. -- Highlights: ► Non‐competitive inhibition of ASCT2 by 1,2,3-dithiazoles was studied in proteoliposomes. ► Different 1,2,3-dithiazoles were synthesized and evaluated as transporter inhibitors. ► Many compounds potently inhibited the glutamine/glutamine antiport catalyzed by ASCT2. ► The inhibition was reversed by DTE indicating reaction with protein Cys. ► The most active compounds gave IC{sub 50} in the range of 3–30 μM.« less
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