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Accession Number:
AD1049173
Title:
Autophagosomal Sequestration of Mitochondria as an Indicator of Antiandrogen Therapy Resistance of Prostate Cancer (PCa)
Corporate Author:
The University of Texas MD Anderson Cancer Center Houston United States
Report Date:
2017-11-01
Abstract:
Purpose We have investigated if sequestration of metabolically dysfunctional mitochondria by theautophagosomes mitophagy imparts anti-androgen resistance. Method Effects of the anti-androgen enzalutamide on the autophagy and mitophagy of androgen-dependentLNCaP and independent C4-2 cells are studied first. Autophagy is monitored by cellular fluorescence incells treated with monodansylcadavarine MDC or stained with anti-LC3B antibody. Cellular Purpose We have investigated if sequestration of metabolically dysfunctional mitochondria by the autophagosomes mitophagy imparts anti-androgen resistance. Method Effects of the anti-androgen enzalutamide on the autophagy and mitophagy of androgen-dependent LNCaP and independent C4-2 cells are studied first. Autophagy is monitored by cellular fluorescence in cells treated with monodansylcadavarine MDC or stained with anti-LC3B antibody. Cellular fluorescence due to Mitosox dye oxidation is used to identify mitochondria producing high superoxide O2-. Mitophagy is monitored using fluorescence resonance energy transfer FRET by visualization of FRET images and quantitation of FRET image intensities using a Nikon A1 or a fluorescence due to Mitosox dye oxidation is used to identify mitochondria producing high superoxide O2-. Mitophagyis monitored using fluorescence resonance energy transfer FRET by visualization of FRET images andquantitation of FRET image intensities using a Nikon A1 or a Leica Di8 fluorescence confocal microscopeand Image J software.Results and Discussion Our data show that the degree of mitophagy is more in androgen-dependent LNCaPcells than in independent C4-2 cells, both growing in androgen-depleted media. Enzalutamide treatmentinduces mitophagy in both cell lines, but the increase in mitophagy is more pronounced in the enzalutamideresistantC4-2 than in the sensitive LNCaP cells.
Descriptive Note:
Technical Report,01 Nov 2016,31 Oct 2017
Pages:
0024
Distribution Statement:
Approved For Public Release;
File Size:
7.80MB
