Vitamin K-3 (VK3) exhibits antitumor activity in rodent and human cancer cells. The relationship between VK3-induced cytotoxicity, and morphological changes in human cervical carcinoma TSGH8302 cells were studied. Cell viability was analyzed by sulforhodamine B protein binding and clonogenic assays. Inhibition of cell growth by VK3 was cell density dependent as measured by IC50 values, which were 17 mu M at 0.5 x 10(4) cells/well and 36 mu M at 1.0 x 10(4) cells/well. Treatment of 10(6) cells with VK3 (5-100 mu M) for 1 h followed by recovery for 24 h caused depletion of the reduced glutathione pool. Under light, fluorescence and scanning electron microscopes, cells showed morphological changes after 1-h treatment with 25 mu M VK3, followed by a 4-h or 12-h recovery. The cells appeared retracted with blebs but no surface microvilli. They exhibited chromatin condensation and DNA fragmentation. Since these phenomena are characteristics of apoptosis, VK3-induced cell death appears to be mediated by apoptosis.

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