Accession Number:

AD1049239

Title:

Autophagosomal Sequestration of Mitochondria as an Indicator of Antiandrogen Therapy Resistance of Prostate Cancer (PCa)

Descriptive Note:

Technical Report,01 Nov 2016,31 Oct 2017

Corporate Author:

The University of Texas MD Anderson Cancer Center Houston United States

Personal Author(s):

• Wilding, George

Report Date:

2017-11-01

Pagination or Media Count:

24.0

Abstract:

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 fluorescencedue 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 Leica Di8 fluorescence confocal microscopeand Image J software. Results and Discussion Our data show that the degree of mitophagy is more in androgen-dependent LNCaP cells than in independent C4-2 cells, both growing in androgen-depleted media. Enzalutamide treatment induces mitophagy in both cell lines, but the increase in mitophagy is more pronounced in the enzalutamide-resistant C4-2 than in the sensitive LNCaP cells. Mitophagy in circulating tumor cells CTCs isolated from patient blood samples are currently being standardized.

Descriptors:

• prostate cancer
• drug resistance
• mitochondria
• androgens
• antibodies
• fluorescence
• resonance
• energy transfer
• cell line
• assays
• confocal microscopy
• immunochemistry
• cytochemistry

Subject Categories:

• Medicine and Medical Research
• Biochemistry

Distribution Statement:

APPROVED FOR PUBLIC RELEASE