Document Detail

G0/G1 arrest and S phase inhibition of human cancer cell lines by inositol hexaphosphate (IP6).
MedLine Citation:
PMID:  11724298     Owner:  NLM     Status:  MEDLINE    
BACKGROUND: Inositol hexaphosphate (InsP6 or IP6) has shown a striking anti-cancer activity in both in vivo and in vitro models. In an attempt to elucidate the mechanism(s) underlying the anti-neoplastic potential of IP6, we investigated its effect on cell cycle progression of MCF-7 estrogen receptor (ER)-positive and MDA-MB 231 ER-negative human breast cancer cell lines and HT-29 human colon cancer cells. METHODS: The anti-proliferative effect of IP6 was evaluated using dual-parameter flow cytometric measurements of DNA content, versus the incorporation of 5-bromo-2-deoxyuridine (BrdU) to determine cells actively synthesizing DNA. Combined analysis of the expression of cell cycle-related proteins, proliferation marker Ki-67 and proliferating cell nuclear antigen (PCNA) versus DNA content were used to determine the amount of proliferating cells in each phase, engaged in cell cycle transit. RESULTS: After 3 days of treatment with 5 mM IP6, S-phase, as estimated by BrdU uptake, was significantly decreased in all three cell lines (p = 0.002). MCF-7 and HT-29 cells accumulated in the G0/G1 range of DNA contents (p = 0.002 and p = 0.001, respectively). MDA MB-231 cells transiently accumulated in G0/G1 only after 2 days (p = 0.01). There was a significant decrease in the percentage of Ki-67 expression in IP6-treated cells, from 82.8+/-3.0% to 66.8+/-4.2% in MCF-7 (p = 0.007), from 93.4+/-4.6% to 71.7+/-3.3% in MDA-MB 231 (p = 0.004), and from 95.2+/-1.2% to 73.5+/-2.5% in HT-29 cells (p = 0.002) respectively. PCNA expression levels were also significantly decreased by IP6 in all three cell lines (MCF-7 p = 0.0007; MDA-MB 231 p = 0.0006; HT-29 p = 0.0001). CONCLUSION: These results show that IP6 controls the progression of cells through the cycle by decreasing S- phase and arresting cells in the G0/G1-phase of the cell cycle. A significant decrease in the expression of proliferation markers indicated that IP6 disengaged cells from actively cycling. Further investigations of cell cycle regulators may lead us to a better understanding of the mechanism(s) of the anti-neoplastic action of IP6.
Y M El-Sherbiny; M C Cox; Z A Ismail; A M Shamsuddin; I Vucenik
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Anticancer research     Volume:  21     ISSN:  0250-7005     ISO Abbreviation:  Anticancer Res.     Publication Date:    2001 Jul-Aug
Date Detail:
Created Date:  2001-11-28     Completed Date:  2001-12-07     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  8102988     Medline TA:  Anticancer Res     Country:  Greece    
Other Details:
Languages:  eng     Pagination:  2393-403     Citation Subset:  IM    
Department of Clinical Pathology University of Minia School of Medicine, Egypt.
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MeSH Terms
Antineoplastic Agents / pharmacology*
Breast Neoplasms / drug therapy,  metabolism,  pathology
Cell Cycle / drug effects*
Cell Cycle Proteins / biosynthesis
Flow Cytometry
G0 Phase / drug effects
G1 Phase / drug effects
HT29 Cells / cytology,  drug effects,  metabolism
Ki-67 Antigen / biosynthesis
Phytic Acid / pharmacology*
Proliferating Cell Nuclear Antigen / biosynthesis
S Phase / drug effects
Tumor Cells, Cultured
Reg. No./Substance:
0/Antineoplastic Agents; 0/Cell Cycle Proteins; 0/Ki-67 Antigen; 0/Proliferating Cell Nuclear Antigen; 83-86-3/Phytic Acid

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