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Biochem Pharmacol. 2004 Jan 15;67(2):337-51.

Cell cycle arrest and autoschizis in a human bladder carcinoma cell line following Vitamin C and Vitamin K3 treatment.

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Department of Urology, College of Medicine, Northeastern Ohio Universities, Summa Health System/NEOUCOM, Akron, OH 44304, USA.


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.

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