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Ultrastruct Pathol. 2014 Oct;38(5):315-28. doi: 10.3109/01913123.2014.927404. Epub 2014 Jun 23.

Pro-oxidant treatment of human prostate carcinoma (DU145) induces autoschizis cell death: autophagosomes build up out of injured endomembranes and mitochondria.

Author information

1
Department of Anatomical Sciences, St Georges' University School of Medicine, KB Taylor Global Scholar's Programme , Newcastle upon Tyne , United Kingdom and.

Abstract

One hour after pro-oxidative treatment by either ascorbate (VC), menadione (VK3), or VC: VK3 combination followed by 24-h incubation in culture medium, DU145 human prostate carcinoma cells developed ultrastructural-dependent organelle damage with the sequence Sham > VC > VK3 > VC: VK3. Along the nuclear alterations and the cytoplasm self-excisions reducing cell size, other induced injuries concerned mitochondria and endomembranes that associated with lysosomes. Damaged organelles surrounded by specialized endoplasmic membranes formed autophagosomes out of phagophores that also captured pieces of glycogen-rich cytoplasm. Most autophagosomes amassed in the diminished-size perikarya and corroborated the enhanced cytotoxicity of the VC: VK3 treatment. These accumulations did not initiate cell death, instead were merely signs of excessive "recycling" of damaged organelles. These features may reflect that high lysosomal activities provided foodstuffs in an ultimate strategy of survival of the tumor cells already devastated by reactive oxidative species (ROS) energetic sites. As such they became transient markers preceding cell death induced to occur by autoschizis and not by apoptosis or other cell deaths. This report could provide more support for the usage of this vitamin combination named APATONE as inexpensive potent adjuvant or treatment in prostate cancers.

KEYWORDS:

Autophagosomes; autoschizis; cell death; endoplasmic reticulum; lysosomes; mitochondria; oxidative stress; prostate carcinoma

PMID:
24955925
DOI:
10.3109/01913123.2014.927404
[Indexed for MEDLINE]

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