Autoschizis: a new form of cell death for human ovarian carcinoma cells following ascorbate:menadione treatment. Nuclear and DNA degradation.
Microscopic aspects, densitometric evaluation of Feulgen-stained DNA, and gel electrophoresis of total DNA have been used to elucidate the effects of 1, 2, and 3 h VC (ascorbic acid), VK3 (menadione), and combined VC:VK3 treatments on the cellular and nuclear morphology and DNA content of a human ovarian carcinoma cell line (MDAH 2774). Optical densitometry showed a significant decrease in cancer cell DNA content directly related to VC and VC:VK3 treatments while VK3 and VC:VK3 treated cells exhibited cytoskeletal changes that included self-excision of cytoplasmic pieces with no membranous organelles. Nuclei decreased in size and exhibited poor contrast consistent with progressive decondensation of their chromatin. Degraded chromatin was also detected in cytoplasmic autophagosomes. Nucleoli segregated their components and fragmented into small pieces. Gel electrophoretic analysis of total DNA revealed evidence of generalized DNA degradation specific to treated tumor cells. These results are consistent with previous observations [Scanning 20 (1998a) 564; Ultrastruct. Pathol. 25 (2001b) 183; J. Histochem. Cytochem. 49 (2001) 109] which demonstrated that the VC:VK3 combination induced autoschizic cell death by a series of cytoplasmic excisions without organelles along with specific nuclear ultrastructural damage.
Gilloteaux
Jacques
J
Department of Anatomy, American University of the Caribbean, School of Medicine, Campus St. Maarten, M.E.I.O. Inc., Ponce de Leon Boulevard 901, Suite #401, Coral Gables, FL 33135, USA. jagillot@yahoo.com
Jamison
James M
JM
Lorimer
Heather E
HE
Jarjoura
David
D
Taper
Henryk S
HS
Calderon
Pedro B
PB
Neal
Deborah R
DR
Summers
Jack L
JL
D000970:Antineoplastic Agents / Q000494:pharmacology; D001205:Ascorbic Acid / Q000494:pharmacology*; D016923:Cell Death / Q000187:drug effects / Q000502:physiology; D002460:Cell Line; D045744:Cell Line, Tumor; D002467:Cell Nucleus / Q000187:drug effects* / Q000473:pathology* / Q000648:ultrastructure; D049109:Cell Proliferation / Q000187:drug effects; D002843:Chromatin / Q000187:drug effects / Q000378:metabolism; D042002:Chromatin Assembly and Disassembly / Q000187:drug effects; D003599:Cytoskeleton / Q000187:drug effects / Q000378:metabolism; D053938:DNA Fragmentation / Q000187:drug effects; D004273:DNA, Neoplasm / Q000378:metabolism* / Q000648:ultrastructure; D005260:Female; D006801:Humans; D007425:Intracellular Membranes / Q000187:drug effects / Q000378:metabolism; D010051:Ovarian Neoplasms / Q000201:enzymology / Q000378:metabolism / Q000473:pathology* / Q000648:ultrastructure; D017382:Reactive Oxygen Species / Q000378:metabolism; D024483:Vitamin K 3 / Q000494:pharmacology*
D000970:Antineoplastic Agents; D002843:Chromatin; D004273:DNA, Neoplasm; D017382:Reactive Oxygen Species; D024483:Vitamin K 3; D001205:Ascorbic Acid