The role of oxidative stress in the development of cisplatin resistance in epithelial ovarian cancer

Jimmy Belotte; Nicole M. Fletcher; Awoniyi O. Awonuga; Mitchell Alexis; Husam M. Abu-Soud; Mohammed G. Saed; Michael P. Diamond; Ghassan M. Saed

doi:10.1177/1933719113503403

The role of oxidative stress in the development of cisplatin resistance in epithelial ovarian cancer

Jimmy Belotte, Nicole M. Fletcher, Awoniyi O. Awonuga, Mitchell Alexis, Husam M. Abu-Soud, Mohammed G. Saed, Michael P. Diamond, Ghassan M. Saed

Research output: Contribution to journal › Article › peer-review

26 Scopus citations

Abstract

Objective: To investigate the role of oxidative stress in the development of cisplatin resistance in epithelial ovarian cancer (EOC). Methods: Two parent EOC cell lines (MDAH-2774 and SKOV-3) and their chemoresistant counterparts (cisplatin, 50 mmol/L) were used. Total RNA was extracted and subjected to real-time reverse transcriptase polymerase chain reaction to evaluate the expression of glutathione reductase (GSR) and inducible nitric oxide synthase (iNOS), as well as nitrate/nitrite levels. Analysis of variance was used for main effects and Tukey for post hoc analysis at P < .05 for statistical significance. Results: Both cisplatin resistant cell lines displayed a significant decrease in GSR messenger RNA (mRNA) levels and activity (P <.01). As compared to sensitive controls, nitrate/nitrite levels were significantly higher in SKOV-3 cisplatin resistant cells while iNOS mRNA levels were significantly higher in MDAH-2774 cisplatin resistant cells (P < .05). Conclusion: Our data suggest that the development of cisplatin resistance tilts the balance toward a pro-oxidant state in EOC.

Original language	English (US)
Pages (from-to)	503-508
Number of pages	6
Journal	Reproductive Sciences
Volume	21
Issue number	4
DOIs	https://doi.org/10.1177/1933719113503403
State	Published - Apr 2014
Externally published	Yes

Keywords

cisplatin resistance
epithelial ovarian cancer
reactive oxygen species

ASJC Scopus subject areas

Obstetrics and Gynecology

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1177/1933719113503403

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title = "The role of oxidative stress in the development of cisplatin resistance in epithelial ovarian cancer",

abstract = "Objective: To investigate the role of oxidative stress in the development of cisplatin resistance in epithelial ovarian cancer (EOC). Methods: Two parent EOC cell lines (MDAH-2774 and SKOV-3) and their chemoresistant counterparts (cisplatin, 50 mmol/L) were used. Total RNA was extracted and subjected to real-time reverse transcriptase polymerase chain reaction to evaluate the expression of glutathione reductase (GSR) and inducible nitric oxide synthase (iNOS), as well as nitrate/nitrite levels. Analysis of variance was used for main effects and Tukey for post hoc analysis at P < .05 for statistical significance. Results: Both cisplatin resistant cell lines displayed a significant decrease in GSR messenger RNA (mRNA) levels and activity (P <.01). As compared to sensitive controls, nitrate/nitrite levels were significantly higher in SKOV-3 cisplatin resistant cells while iNOS mRNA levels were significantly higher in MDAH-2774 cisplatin resistant cells (P < .05). Conclusion: Our data suggest that the development of cisplatin resistance tilts the balance toward a pro-oxidant state in EOC.",

keywords = "cisplatin resistance, epithelial ovarian cancer, reactive oxygen species",

author = "Jimmy Belotte and Fletcher, {Nicole M.} and Awonuga, {Awoniyi O.} and Mitchell Alexis and Abu-Soud, {Husam M.} and Saed, {Mohammed G.} and Diamond, {Michael P.} and Saed, {Ghassan M.}",

note = "Funding Information: The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: This project was funded by NIH/NICHD grant K12HD001254 .",

year = "2014",

month = apr,

doi = "10.1177/1933719113503403",

language = "English (US)",

volume = "21",

pages = "503--508",

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T1 - The role of oxidative stress in the development of cisplatin resistance in epithelial ovarian cancer

AU - Belotte, Jimmy

AU - Fletcher, Nicole M.

AU - Awonuga, Awoniyi O.

AU - Alexis, Mitchell

AU - Abu-Soud, Husam M.

AU - Saed, Mohammed G.

AU - Diamond, Michael P.

AU - Saed, Ghassan M.

N1 - Funding Information: The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: This project was funded by NIH/NICHD grant K12HD001254 .

PY - 2014/4

Y1 - 2014/4

N2 - Objective: To investigate the role of oxidative stress in the development of cisplatin resistance in epithelial ovarian cancer (EOC). Methods: Two parent EOC cell lines (MDAH-2774 and SKOV-3) and their chemoresistant counterparts (cisplatin, 50 mmol/L) were used. Total RNA was extracted and subjected to real-time reverse transcriptase polymerase chain reaction to evaluate the expression of glutathione reductase (GSR) and inducible nitric oxide synthase (iNOS), as well as nitrate/nitrite levels. Analysis of variance was used for main effects and Tukey for post hoc analysis at P < .05 for statistical significance. Results: Both cisplatin resistant cell lines displayed a significant decrease in GSR messenger RNA (mRNA) levels and activity (P <.01). As compared to sensitive controls, nitrate/nitrite levels were significantly higher in SKOV-3 cisplatin resistant cells while iNOS mRNA levels were significantly higher in MDAH-2774 cisplatin resistant cells (P < .05). Conclusion: Our data suggest that the development of cisplatin resistance tilts the balance toward a pro-oxidant state in EOC.

AB - Objective: To investigate the role of oxidative stress in the development of cisplatin resistance in epithelial ovarian cancer (EOC). Methods: Two parent EOC cell lines (MDAH-2774 and SKOV-3) and their chemoresistant counterparts (cisplatin, 50 mmol/L) were used. Total RNA was extracted and subjected to real-time reverse transcriptase polymerase chain reaction to evaluate the expression of glutathione reductase (GSR) and inducible nitric oxide synthase (iNOS), as well as nitrate/nitrite levels. Analysis of variance was used for main effects and Tukey for post hoc analysis at P < .05 for statistical significance. Results: Both cisplatin resistant cell lines displayed a significant decrease in GSR messenger RNA (mRNA) levels and activity (P <.01). As compared to sensitive controls, nitrate/nitrite levels were significantly higher in SKOV-3 cisplatin resistant cells while iNOS mRNA levels were significantly higher in MDAH-2774 cisplatin resistant cells (P < .05). Conclusion: Our data suggest that the development of cisplatin resistance tilts the balance toward a pro-oxidant state in EOC.

KW - cisplatin resistance

KW - epithelial ovarian cancer

KW - reactive oxygen species

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The role of oxidative stress in the development of cisplatin resistance in epithelial ovarian cancer

Abstract

Keywords

ASJC Scopus subject areas

UN SDGs

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