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.
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.
Zhang
Mei
M
Department of Biology, The Chinese University of Hong Kong, Hong Kong, P.R. China.
Chiu
Lawrence C-M
LC
Cheung
Peter C K
PC
Ooi
Vincent E C
VE
D017209:Apoptosis / Q000187:drug effects; D001943:Breast Neoplasms / Q000378:metabolism / Q000473:pathology; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects; D019938:Cyclin D1 / Q000096:biosynthesis; D019927:Cyclin E / Q000096:biosynthesis; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation / Q000187:drug effects; D005260:Female; D005434:Flow Cytometry; D006131:Growth Inhibitors / Q000302:isolation & purification / Q000494:pharmacology; D006801:Humans; D015151:Immunoblotting; D025282:Mycelium / Q000737:chemistry*; D020072:Polyporales / Q000737:chemistry*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000096:biosynthesis; D013997:Time Factors; D051028:bcl-2-Associated X Protein / Q000096:biosynthesis; D047071:beta-Glucans / Q000302:isolation & purification / Q000494:pharmacology*
C494826:BAX protein, human; D019927:Cyclin E; D006131:Growth Inhibitors; C509300:PCM3-II; D019253:Proto-Oncogene Proteins c-bcl-2; D051028:bcl-2-Associated X Protein; D047071:beta-Glucans; D019938:Cyclin D1