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Growth-inhibitory effects of a beta-glucan from the mycelium of Poria cocos on human breast carcinoma MCF-7 cells: cell-cycle arrest and apoptosis induction.

Abstract
Because of the reported immune-enhancing and anti-tumor activities of some mushroom polysaccharides, their applications as biological response modifiers have attracted significant attention. We have purified a water-soluble beta-glucan PCM3-II, comprising mainly 1right curved arrow 3 and 1right curved arrow 4 linkages, from the mycelia of Poria cocos (Schw.) Wolf (Fu-ling). In this study, the growth-inhibitory effect of PCM3-II was further explored on the human breast carcinoma MCF-7 cells in vitro. The dose effect of PCM3-II was studied by incubating the breast cancer cells with 12.5-400 microg/ml of the glucan for 72 h. The MTT study showed that PCM3-II reduced proliferation and viability of the MCF-7 cells dose-dependently, so that the cancer-cell growth was decreased by 50% of the control level at 400 microg/ml of the glucan. The time effect of PCM3-II was then investigated by treating the breast cancer cells with 400 microg/ml of the glucan for 24, 48 and 72 h, respectively. Results from the flow cytometry study demonstrated that PCM3-II induced cell-cycle G1 arrest time-dependently and about 90% of the cells in cell cycle were accumulated at G1 phase after 72 h of treatment. The G1 arrest was associated with downregulations of the unscheduled cyclin D1 and cyclin E expressions in the breast cancer cells. Apoptosis was also induced by PCM3-II in the MCF-7 cells, so that the subG1 cells in DNA histogram of the flow cytometry were elevated by 5-fold of the control level at 48 h and by 24-fold at 72 h of treatment. The immunoblot study also showed that the glucan induced depletion of the antiapoptotic Bcl-2 protein, but not the proapoptotic Bax protein, so that the Bax/Bcl-2 ratio was elevated in the breast cancer cells at the time when the most prominent apoptosis was also observed. In conclusion, although the detailed mechanism for the anti-tumor activity of the P. cocos beta-glucan still needs further investigation, this study provides preliminary insights into its mode of action and perspectives of its development as a water-soluble anti-tumor agent.
AuthorsMei Zhang, Lawrence C-M Chiu, Peter C K Cheung, Vincent E C Ooi
JournalOncology reports (Oncol Rep) Vol. 15 Issue 3 Pg. 637-43 (Mar 2006) ISSN: 1021-335X [Print] Greece
PMID16465424 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • BAX protein, human
  • Cyclin E
  • Growth Inhibitors
  • PCM3-II
  • Proto-Oncogene Proteins c-bcl-2
  • bcl-2-Associated X Protein
  • beta-Glucans
  • Cyclin D1
Topics
  • Apoptosis (drug effects)
  • Breast Neoplasms (metabolism, pathology)
  • Cell Cycle (drug effects)
  • Cell Line, Tumor
  • Cell Proliferation (drug effects)
  • Cell Survival (drug effects)
  • Cyclin D1 (biosynthesis)
  • Cyclin E (biosynthesis)
  • Dose-Response Relationship, Drug
  • Down-Regulation (drug effects)
  • Female
  • Flow Cytometry
  • Growth Inhibitors (isolation & purification, pharmacology)
  • Humans
  • Immunoblotting
  • Mycelium (chemistry)
  • Polyporales (chemistry)
  • Proto-Oncogene Proteins c-bcl-2 (biosynthesis)
  • Time Factors
  • bcl-2-Associated X Protein (biosynthesis)
  • beta-Glucans (isolation & purification, pharmacology)

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