A Redox-active Mn Porphyrin, MnTnBuOE-2-PyP<sup>5+</sup>, Synergizes with Carboplatin in Treatment of Chemoresistant Ovarian Cell Line
Issued Date
2022-01-01
Resource Type
ISSN
19420900
eISSN
19420994
Scopus ID
2-s2.0-85135202368
Pubmed ID
35898616
Journal Title
Oxidative Medicine and Cellular Longevity
Volume
2022
Rights Holder(s)
SCOPUS
Bibliographic Citation
Oxidative Medicine and Cellular Longevity Vol.2022 (2022)
Suggested Citation
Chaiswing L., Yarana C., St. Clair W., Tovmasyan A., Batinic-Haberle I., Spasojevic I., St. Clair D. A Redox-active Mn Porphyrin, MnTnBuOE-2-PyP<sup>5+</sup>, Synergizes with Carboplatin in Treatment of Chemoresistant Ovarian Cell Line. Oxidative Medicine and Cellular Longevity Vol.2022 (2022). doi:10.1155/2022/9664636 Retrieved from: https://repository.li.mahidol.ac.th/handle/20.500.14594/83892
Title
A Redox-active Mn Porphyrin, MnTnBuOE-2-PyP<sup>5+</sup>, Synergizes with Carboplatin in Treatment of Chemoresistant Ovarian Cell Line
Other Contributor(s)
Abstract
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.