Synergistic Antitumor Cytotoxic Actions of Ascorbate and Menadione on Human Prostate (DU145) Cancer Cells In Vitro: Nucleus and Other Injuries Preceding Cell Death by Autoschizis

Gilloteaux, Jacques, Jamison, James, Neal, Deborah and Summers, Jack (2014) Synergistic Antitumor Cytotoxic Actions of Ascorbate and Menadione on Human Prostate (DU145) Cancer Cells In Vitro: Nucleus and Other Injuries Preceding Cell Death by Autoschizis. Ultrastructural Pathology, 38 (2). pp. 116-140. ISSN 0191-3123

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Abstract

Scanning (SEM) and transmission electron microscopy (TEM) were used to characterize the cytotoxic effects of ascorbate (VC), menadione (VK3), or a VC:VK3 combination on a human prostate carcinoma cell line (DU145) following a 1-h vitamin treatment and a subsequent 24-h incubation in culture medium. Cell alterations examined by light and electron microscopy were treatment-dependent with VC + VK3 >VK3 > VC > Sham. Oxidative stress-induced damage was found in most organelles. This report describes injuries in the tumor cell nucleus (chromatin and nucleolus), mitochondria, endomembranes, lysosomal bodies (autophagocytoses) and inclusions. Morphologic alterations suggest that cytoskeleton damage is likely responsible for the superficial cytoplasmic changes, including major changes in cell shape and size and the self-excising phenomena. Unlike apoptotic bodies, the excised pieces contain ribonucleoproteins, but not organelles. These deleterious events cause a progressive, significant reduction in the tumor cell size. During nuclear alterations, the nuclei maintain their envelope during chromatolysis and karyolysis until cell death, while nucleoli undergo a characteristic segregation of their components. In addition, changes in fat and glycogen storage are consistent the cytotoxic and metabolic alterations caused by the respective treatments. All cellular ultrastructural changes are consistent with cell death by autoschizis and not apoptosis or other kinds of cell death.

Item Type:	Article
Additional Information:	PMID: 24460713
Uncontrolled Keywords:	carcinoma, organelles
Subjects:	B100 Anatomy, Physiology and Pathology C100 Biology
Department:	Faculties > Health and Life Sciences > Applied Sciences
Depositing User:	Ay Okpokam
Date Deposited:	12 May 2014 11:45
Last Modified:	12 Oct 2019 18:28
URI:	http://nrl.northumbria.ac.uk/id/eprint/16411

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