Androgen-Induced Oxidative Stress in Human LNCaP Prostate Cancer Cells Is Associated with Multiple Mitochondrial Modifications

Maureen O. Ripple, Kevork Hagopian, Terry D. Oberley, Heide Schatten, Richard Weindruch

Research output: Contribution to journalArticle

35 Citations (Scopus)

Abstract

We investigated the role of androgen-induced oxidative stress in prostate cancer using the androgen-responsive LNCaP human prostate cancer cell line exposed to a 1-nM concentration of the synthetic androgen R1881 (which correlates with serum androgen levels). Such exposure, which decreases growth rate and increases oxidative stress in LNCaP cells, induced statistically significant mitochondrial changes. A 40% increase in 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide (MTT) reduction, indicative of mitochondrial dehydrogenase activity, occurred 24 hr after androgen treatment. This change preceded 50-110% increases, 40-96 hr after R1881 exposure, in levels of cellular peroxides and hydroxyl radicals as measured by 2′7′-dicholorofluorescin diacetate (DCF) fluorescence. On the basis of electron microscopy measurements, R1881 treatment increased the area fraction of mitochondria per cell by ∼100% at 72 hr. In agreement, mitochondrial mass at 96 hr, evaluated by the fluorescent dye nonyl acridine orange (NAO), was 80% higher in treated cells. R1881 exposure for 24 hr lowered the activities of electron transport system (ETS) complexes, I, II, and IV by 17-27% and ATP levels by 50%. The ETS inhibitors, rotenone and antimycin A, lowered androgen-induced DCF fluorescence readings to control levels thereby suggesting ETS involvement in androgen-induced oxidant production. Addition of α-tocopherol succinate abrogated R1881-induced elevations in MTT reduction. In sum, androgens may, directly or indirectly, contribute to oxidative stress in LNCaP cells by regulating mitochondrial number, activity, and oxidant production by mechanisms that are, at least in part, sensitive to an antioxidant.

Original languageEnglish (US)
Pages (from-to)71-81
Number of pages11
JournalAntioxidants and Redox Signaling
Volume1
Issue number1
DOIs
StatePublished - Jan 1 1999
Externally publishedYes

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Oxidative stress
Metribolone
Androgens
Prostatic Neoplasms
Oxidative Stress
Cells
Electron Transport
Oxidants
Testosterone Congeners
Fluorescence
Antimycin A
Electron Transport Complex I
Rotenone
Acridine Orange
Mitochondria
Level control
Peroxides
alpha-Tocopherol
Fluorescent Dyes
Hydroxyl Radical

ASJC Scopus subject areas

  • Biochemistry
  • Physiology
  • Molecular Biology
  • Clinical Biochemistry
  • Cell Biology

Cite this

Androgen-Induced Oxidative Stress in Human LNCaP Prostate Cancer Cells Is Associated with Multiple Mitochondrial Modifications. / Ripple, Maureen O.; Hagopian, Kevork; Oberley, Terry D.; Schatten, Heide; Weindruch, Richard.

In: Antioxidants and Redox Signaling, Vol. 1, No. 1, 01.01.1999, p. 71-81.

Research output: Contribution to journalArticle

Ripple, Maureen O. ; Hagopian, Kevork ; Oberley, Terry D. ; Schatten, Heide ; Weindruch, Richard. / Androgen-Induced Oxidative Stress in Human LNCaP Prostate Cancer Cells Is Associated with Multiple Mitochondrial Modifications. In: Antioxidants and Redox Signaling. 1999 ; Vol. 1, No. 1. pp. 71-81.
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