Document Detail

Cell cycle arrest and autoschizis in a human bladder carcinoma cell line following Vitamin C and Vitamin K3 treatment.
MedLine Citation:
PMID:  14698046     Owner:  NLM     Status:  MEDLINE    
Exponentially growing cultures of human bladder tumor cells (T24) were treated with Vitamin C (VC) alone, Vitamin K(3) (VK(3)) alone, or with a VC:VK(3) combination for 1, 2, or 4hr. Flow cytometry of T24 cells exposed to the vitamins for 1h revealed a growth arrested population and a population undergoing cell death. Cells in G(1) during vitamin treatment arrested in G(1) while those in S phase progressed through S phase and arrested in G(2)/M. DNA synthesis decreased to 14 to 21% of control levels which agreed with the percent of cells in S phase during treatment. Annexin V labeling demonstrated the majority of the cells died by autoschizis, but necrosis and apoptosis also were observed. Catalase treatment abrogated both cell cycle arrest and cell death which implicated hydrogen peroxide (H(2)O(2)) in these processes. Redox cycling of VC and VK(3) increased H(2)O(2) production and decreased cellular thiol levels and DNA content, while increasing intracellular Ca(2+) levels and lipid peroxidation. Feulgen staining of treated cells revealed a time-dependent decrease in tumor cell DNA, while electrophoresis revealed a spread pattern. These results suggest that Ca(2+) disregulation activates at least one DNase which degrades tumor cell DNA and induces tumor cell death.
James M Jamison; Jacques Gilloteaux; M Reza Nassiri; Meenakshi Venugopal; Deborah R Neal; Jack L Summers
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Biochemical pharmacology     Volume:  67     ISSN:  0006-2952     ISO Abbreviation:  Biochem. Pharmacol.     Publication Date:  2004 Jan 
Date Detail:
Created Date:  2003-12-30     Completed Date:  2004-02-11     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  0101032     Medline TA:  Biochem Pharmacol     Country:  England    
Other Details:
Languages:  eng     Pagination:  337-51     Citation Subset:  IM    
Department of Urology, College of Medicine, Northeastern Ohio Universities, Summa Health System/NEOUCOM, Akron, OH 44304, USA.
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MeSH Terms
Antioxidants / pharmacology*
Ascorbic Acid / pharmacology*
Calcium / metabolism
Cell Cycle / drug effects*
DNA, Neoplasm / drug effects
Flow Cytometry
Hydrogen Peroxide / metabolism
Sulfhydryl Compounds / metabolism
Tumor Cells, Cultured
Urinary Bladder Neoplasms / pathology
Vitamin K 3 / pharmacology*
Reg. No./Substance:
0/Antioxidants; 0/DNA, Neoplasm; 0/Sulfhydryl Compounds; 50-81-7/Ascorbic Acid; 58-27-5/Vitamin K 3; 7440-70-2/Calcium; 7722-84-1/Hydrogen Peroxide

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