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A Redox-active Mn Porphyrin, MnTnBuOE-2-PyP5+, Synergizes with Carboplatin in Treatment of Chemoresistant Ovarian Cell Line.

Publication ,  Journal Article
Chaiswing, L; Yarana, C; St Clair, W; Tovmasyan, A; Batinic-Haberle, I; Spasojevic, I; St Clair, D
Published in: Oxid Med Cell Longev
2022

We have employed a redox-active MnP (MnTnBuOE-2-PyP5+, Mn(III) meso-tetrakis (N-n-butoxyethylpyridinium-2-yl) porphyrin) frequently identified as superoxide dismutase mimic or BMX-001, to explore the redox status of normal ovarian cell in relation to two ovarian cancer cell lines: OV90 human serous ovarian cancer cell and chemotherapy-resistant OV90 cell (OVCD). We identified that OVCD cells are under oxidative stress due to high hydrogen peroxide (H2O2) levels and low glutathione peroxidase and thioredoxin 1. Furthermore, OVCD cells have increased glycolysis activity and mitochondrial respiration when compared to immortalized ovarian cells (hTER7) and parental cancer cells (OV90). Our goal was to study how ovarian cell growth depends upon the redox state of the cell; hence, we used MnP (BMX-001), a redox-active MnSOD mimetic, as a molecular tool to alter ovarian cancer redox state. Interestingly, OVCD cells preferentially uptake MnP relative to OV90 cells which led to increased inhibition of cell growth, glycolytic activity, OXPHOS, and ATP, in OVCD cells. These effects were further increased when MnP was combined with carboplatin. The effects were discussed with regard to the elevation in H2O2 levels, increased oxidative stress, and reduced Nrf2 levels and its downstream targets when cells were exposed to either MnP or MnP/carboplatin. It is significant to emphasize that MnP protects normal ovarian cell line, hTER7, against carboplatin toxicity. Our data demonstrate that the addition of MnP-based redox-active drugs may be used (via increasing excessively the oxidative stress of serous ovarian cancer cells) to improve cancer patients' chemotherapy outcomes, which develop resistance to platinum-based drugs.

Duke Scholars

Published In

Oxid Med Cell Longev

DOI

EISSN

1942-0994

Publication Date

2022

Volume

2022

Start / End Page

9664636

Location

United States

Related Subject Headings

  • Superoxide Dismutase
  • Porphyrins
  • Oxidation-Reduction
  • Ovarian Neoplasms
  • Metalloporphyrins
  • Hydrogen Peroxide
  • Humans
  • Female
  • Cell Line
  • Carboplatin
 

Citation

APA
Chicago
ICMJE
MLA
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Chaiswing, L., Yarana, C., St Clair, W., Tovmasyan, A., Batinic-Haberle, I., Spasojevic, I., & St Clair, D. (2022). A Redox-active Mn Porphyrin, MnTnBuOE-2-PyP5+, Synergizes with Carboplatin in Treatment of Chemoresistant Ovarian Cell Line. Oxid Med Cell Longev, 2022, 9664636. https://doi.org/10.1155/2022/9664636
Chaiswing, Luksana, Chontida Yarana, William St Clair, Artak Tovmasyan, Ines Batinic-Haberle, Ivan Spasojevic, and Daret St Clair. “A Redox-active Mn Porphyrin, MnTnBuOE-2-PyP5+, Synergizes with Carboplatin in Treatment of Chemoresistant Ovarian Cell Line.Oxid Med Cell Longev 2022 (2022): 9664636. https://doi.org/10.1155/2022/9664636.
Chaiswing L, Yarana C, St Clair W, Tovmasyan A, Batinic-Haberle I, Spasojevic I, et al. A Redox-active Mn Porphyrin, MnTnBuOE-2-PyP5+, Synergizes with Carboplatin in Treatment of Chemoresistant Ovarian Cell Line. Oxid Med Cell Longev. 2022;2022:9664636.
Chaiswing, Luksana, et al. “A Redox-active Mn Porphyrin, MnTnBuOE-2-PyP5+, Synergizes with Carboplatin in Treatment of Chemoresistant Ovarian Cell Line.Oxid Med Cell Longev, vol. 2022, 2022, p. 9664636. Pubmed, doi:10.1155/2022/9664636.
Chaiswing L, Yarana C, St Clair W, Tovmasyan A, Batinic-Haberle I, Spasojevic I, St Clair D. A Redox-active Mn Porphyrin, MnTnBuOE-2-PyP5+, Synergizes with Carboplatin in Treatment of Chemoresistant Ovarian Cell Line. Oxid Med Cell Longev. 2022;2022:9664636.

Published In

Oxid Med Cell Longev

DOI

EISSN

1942-0994

Publication Date

2022

Volume

2022

Start / End Page

9664636

Location

United States

Related Subject Headings

  • Superoxide Dismutase
  • Porphyrins
  • Oxidation-Reduction
  • Ovarian Neoplasms
  • Metalloporphyrins
  • Hydrogen Peroxide
  • Humans
  • Female
  • Cell Line
  • Carboplatin