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

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Exponentially growing cultures of human bladder tumor cells (T24) were treated with Vitamin C (VC) alone, Vitamin K3 (VK3) alone, or with a VC:VK3 combination for 1, 2, or 4 hr. Flow cytometry of T24 cells exposed to the vitamins for 1 h revealed a growth arrested population and a population undergoing cell death. Cells in G1 during vitamin treatment arrested in G1 while those in S phase progressed through S phase and arrested in G2/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 (H2O2) in these processes. Redox cycling of VC and VK3 increased H2O2 production and decreased cellular thiol levels and DNA content, while increasing intracellular Ca2+ 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 Ca2+ disregulation activates at least one DNase which degrades tumor cell DNA and induces tumor cell death.

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