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Proceedings Paper

Microscopic analysis of cell death by metabolic stress-induced autophagy in prostate cancer
Author(s): Chun Changou; R. Holland Cheng; Richard Bold; Hsing-Jien Kung; Frank Y. S. Chuang
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Paper Abstract

Autophagy is an intracellular recycling mechanism that helps cells to survive against environmental stress and nutritional starvation. We have recently shown that prostate cancers undergo metabolic stress and caspase-independent cell death following exposure to arginine deiminase (ADI, an enzyme that degrades arginine in tissue). The aims of our current investigation into the application of ADI as a novel cancer therapy are to identify the components mediating tumor cell death, and to determine the role of autophagy (stimulated by ADI and/or rapamycin) on cell death. Using advanced fluorescence microscopy techniques including 3D deconvolution and superresolution structured-illumination microscopy (SIM), we show that prostate tumor cells that are killed after exposure to ADI for extended periods, exhibit a morphology that is distinct from caspase-dependent apoptosis; and that autophagosomes forming as a result of ADI stimulation contain DAPI-stained nuclear material. Fluorescence imaging (as well as cryo-electron microscopy) show a breakdown of both the inner and outer nuclear membranes at the interface between the cell nucleus and aggregated autophagolysosomes. Finally, the addition of N-acetyl cysteine (or NAC, a scavenger for reactive oxygen species) effectively abolishes the appearance of autophagolysosomes containing nuclear material. We hope to continue this research to understand the processes that govern the survival or death of these tumor cells, in order to develop methods to improve the efficacy of cancer pharmacotherapy.

Paper Details

Date Published: 22 February 2013
PDF: 7 pages
Proc. SPIE 8587, Imaging, Manipulation, and Analysis of Biomolecules, Cells, and Tissues XI, 85870D (22 February 2013); doi: 10.1117/12.2004759
Show Author Affiliations
Chun Changou, Univ. of California, Davis (United States)
R. Holland Cheng, Univ. of California, Davis (United States)
Richard Bold, Univ. of California, Davis (United States)
Hsing-Jien Kung, Univ. of California Davis Medical Ctr. (United States)
Frank Y. S. Chuang, Univ. of California, Davis (United States)

Published in SPIE Proceedings Vol. 8587:
Imaging, Manipulation, and Analysis of Biomolecules, Cells, and Tissues XI
Daniel L. Farkas; Dan V. Nicolau; Robert C. Leif, Editor(s)

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