Microscopic analysis of cell death by metabolic stress-induced autophagy in prostate cancer

Chun Changou, R. Holland Cheng, Richard Bold, Hsing Jien Kung, Frank Y S Chuang

研究成果: 書貢獻/報告類型會議貢獻

摘要

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.
原文英語
主出版物標題Imaging, Manipulation, and Analysis of Biomolecules, Cells, and Tissues XI
8587
DOIs
出版狀態已發佈 - 五月 27 2013
對外發佈
事件Imaging, Manipulation, and Analysis of Biomolecules, Cells, and Tissues XI - San Francisco, CA, 美国
持續時間: 二月 2 2013二月 5 2013

會議

會議Imaging, Manipulation, and Analysis of Biomolecules, Cells, and Tissues XI
國家/地區美国
城市San Francisco, CA
期間2/2/132/5/13

ASJC Scopus subject areas

  • 原子與分子物理與光學
  • 電子、光磁材料
  • 生物材料
  • 放射學、核子醫學和影像學

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