Microscopic aspects of autoschizic cell death in human ovarian carcinoma (2774) cells following vitamin C, vitamin K₃ or vitamin C: K ₃ treatment

Human ovarian carcinoma cells (MDAH 2774) were treated with sodium ascorbate (VC), menadione (VK₃), or with a VC:VK₃ combination for 1 h and then studied using light microscopy (LM) and scanning (SEM) and transmission electron (TEM) microscopy. Plasma membrane damage (blisters and blebs, hairy aspect) results from vitamin C (VC) treatment, while cytoskeletal damage and self-morsellation are caused by vitamin K₃ (VK₃) treatment. VC:VK₃-treated cells exhibit exacerbated injuries characteristic of both VC and VK₃ treatment as well as a significant decrease in cell diameters from 20-35 μm for control cells to 7-12 μm for VC:VK₃ treatment. Moreover, after a 1-h exposure to the vitamin combination, autoschizis (43%), apoptosis (3%), and oncosis (1.9%) are observed at the percentages indicated. All cellular changes associated with autoschizis observed with SEM were confirmed by LM and TEM observations and are consistent with cell death by autoschizis: decrease in cell size, cytoplasmic self-excisions, degradation of the nucleus and nucleolus without formation of apoptotic bodies and, ultimately, karyorrhexis and karyolysis. These results also suggest that the vitamin combination may find clinical use in the treatment of ovarian cancer.