Alpha-lipoic acid modulates ovarian surface epithelial cell growth

E. Vig-Varga, Eric A. Benson, Tony L. Limbil, Bernadette M. Allison, Mark G. Goebl, Maureen A. Harrington

Research output: Contribution to journalArticle

16 Citations (Scopus)

Abstract

Objective.: The intracellular redox state plays an important role in controlling inflammation. Clinical and laboratory data suggest that inflammation can lead to tumor progression. We hypothesized that restoring intracellular redox control would inhibit inflammation and subsequently tumor progression. Our studies were designed to investigate the effect of alpha-lipoic acid (ALA), a naturally occurring antioxidant, on a key inflammatory signaling pathway and cell proliferation in normal and tumorigenic ovarian surface epithelial cells. Methods.: Normal and tumorigenic ovarian surface epithelial cells were isolated as described by Roby and coworkers [Roby KF, Taylor CC, Sweetwood JP, Cheng Y, Pace JL, Tawpik O, Persons DL, Smith PG, Terranova PF, Development of a syngeneic mouse model for events related to ovarian cancer. Carcinogen 2000;21 (4):585. [1]]. The effect of ALA on cellular function was measured in cell proliferation and apoptosis assays. p27kip1 protein levels were measured by Western analysis. Activation of NF-κB dependent transcription was assessed in cell cultures transiently transfected with NF-κB controlled reporter constructs. Results.: Our results reveal that ALA selectively inhibits the growth of tumorigenic as compared to non-tumorigenic ovarian surface epithelial cells. The growth inhibitory effect of ALA is not due to induction of apoptosis but instead is associated with an increase in the half-life of the cyclin-dependent kinase inhibitor, p27kip1. In parallel to the growth inhibitory effect, ALA also affects a key inflammatory signaling pathway by inhibiting TNFα-induced NF-κB signaling activity. Conclusions.: Our studies are the first to show that ALA treatment has a growth inhibitory effect on malignant surface epithelial cells of ovarian origin. We have also confirmed the reproducibility of the immunocompetent mouse ovarian cancer model originally described by Roby and coworkers [Roby KF, Taylor CC, Sweetwood JP, Cheng Y, Pace JL, Tawpik O, Persons DL, Smith PG, Terranova PF, Development of a syngeneic mouse model for events related to ovarian cancer. Carcinogen 2000;21 (4):585. [1]].

Original languageEnglish (US)
Pages (from-to)45-52
Number of pages8
JournalGynecologic Oncology
Volume103
Issue number1
DOIs
StatePublished - Oct 1 2006

Fingerprint

Thioctic Acid
Epithelial Cells
Growth
Ovarian Neoplasms
Inflammation
Carcinogens
Oxidation-Reduction
Cell Proliferation
Cyclin-Dependent Kinase Inhibitor p27
Apoptosis
Cyclin-Dependent Kinases
Half-Life
Neoplasms
Cell Culture Techniques
Antioxidants

Keywords

  • Alpha-lipoic acid (ALA)
  • Apoptosis
  • Inflammation
  • Nuclear factor-κB (NF-κB)
  • Ovarian cancer
  • Ovarian surface epithelial cells
  • p27
  • Tumor necrosis factor alpha (TNFα)

ASJC Scopus subject areas

  • Obstetrics and Gynecology
  • Oncology

Cite this

Alpha-lipoic acid modulates ovarian surface epithelial cell growth. / Vig-Varga, E.; Benson, Eric A.; Limbil, Tony L.; Allison, Bernadette M.; Goebl, Mark G.; Harrington, Maureen A.

In: Gynecologic Oncology, Vol. 103, No. 1, 01.10.2006, p. 45-52.

Research output: Contribution to journalArticle

Vig-Varga, E. ; Benson, Eric A. ; Limbil, Tony L. ; Allison, Bernadette M. ; Goebl, Mark G. ; Harrington, Maureen A. / Alpha-lipoic acid modulates ovarian surface epithelial cell growth. In: Gynecologic Oncology. 2006 ; Vol. 103, No. 1. pp. 45-52.
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AU - Goebl, Mark G.

AU - Harrington, Maureen A.

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