Cell death by autoschizis in TRAMP prostate carcinoma cells as a result of treatment by ascorbate: menadione combination.

A prostate carcinoma cell line derived from the transgenic murine prostate cancer model (TRAMP) was treated with ascorbate (VC) alone, menadione (VK(3)) alone, or a combination of ascorbate:menadione (VC + VK(3)) for 1, 2, and 4 h. Cytotoxic cell alterations examined by light and electron microscopy were treatment-dependent with VC + VK(3) > VC > VK(3). Induced by oxidative stress, these alterations included cytokeletal changes conducive to cytoplasmic blebbing, self-excisions, and progressive nuclear alterations. While the excised parts contained ribosomes, they were devoid of nuclear fragments or other organelles. The organelle-free self-excisions caused an extreme reduction in cell size as well as chromatolysis and karyolysis that were consistent with cell death by autoschizis, but not with apoptosis.