Preclinical therapeutic potential of a nitrosylating agent in the treatment of ovarian cancer.

This study examines the role of s-nitrosylation in the growth of ovarian cancer using cell culture based and in vivo approaches. Using the nitrosylating agent, S-nitrosoglutathione (GSNO), a physiological nitric oxide molecule, we show that GSNO treatment inhibited proliferation of chemoresponsive a...

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Autores principales:	Shailendra Giri, Ramandeep Rattan, Mandar Deshpande, Jacie L Maguire, Zachary Johnson, Rondell P Graham, Viji Shridhar
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2014
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/04204642a0234a30a6fe94cde88ff8e4
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spelling	oai:doaj.org-article:04204642a0234a30a6fe94cde88ff8e42021-11-18T08:17:32ZPreclinical therapeutic potential of a nitrosylating agent in the treatment of ovarian cancer.1932-620310.1371/journal.pone.0097897https://doaj.org/article/04204642a0234a30a6fe94cde88ff8e42014-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/24887420/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203This study examines the role of s-nitrosylation in the growth of ovarian cancer using cell culture based and in vivo approaches. Using the nitrosylating agent, S-nitrosoglutathione (GSNO), a physiological nitric oxide molecule, we show that GSNO treatment inhibited proliferation of chemoresponsive and chemoresistant ovarian cancer cell lines (A2780, C200, SKVO3, ID8, OVCAR3, OVCAR4, OVCAR5, OVCAR7, OVCAR8, OVCAR10, PE01 and PE04) in a dose dependent manner. GSNO treatment abrogated growth factor (HB-EGF) induced signal transduction including phosphorylation of Akt, p42/44 and STAT3, which are known to play critical roles in ovarian cancer growth and progression. To examine the therapeutic potential of GSNO in vivo, nude mice bearing intra-peritoneal xenografts of human A2780 ovarian carcinoma cell line (2 × 10(6)) were orally administered GSNO at the dose of 1 mg/kg body weight. Daily oral administration of GSNO significantly attenuated tumor mass (p<0.001) in the peritoneal cavity compared to vehicle (phosphate buffered saline) treated group at 4 weeks. GSNO also potentiated cisplatin mediated tumor toxicity in an A2780 ovarian carcinoma nude mouse model. GSNO's nitrosylating ability was reflected in the induced nitrosylation of various known proteins including NFκB p65, Akt and EGFR. As a novel finding, we observed that GSNO also induced nitrosylation with inverse relationship at tyrosine 705 phosphorylation of STAT3, an established player in chemoresistance and cell proliferation in ovarian cancer and in cancer in general. Overall, our study underlines the significance of S-nitrosylation of key cancer promoting proteins in modulating ovarian cancer and proposes the therapeutic potential of nitrosylating agents (like GSNO) for the treatment of ovarian cancer alone or in combination with chemotherapeutic drugs.Shailendra GiriRamandeep RattanMandar DeshpandeJacie L MaguireZachary JohnsonRondell P GrahamViji ShridharPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 9, Iss 6, p e97897 (2014)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Shailendra Giri Ramandeep Rattan Mandar Deshpande Jacie L Maguire Zachary Johnson Rondell P Graham Viji Shridhar Preclinical therapeutic potential of a nitrosylating agent in the treatment of ovarian cancer.
description	This study examines the role of s-nitrosylation in the growth of ovarian cancer using cell culture based and in vivo approaches. Using the nitrosylating agent, S-nitrosoglutathione (GSNO), a physiological nitric oxide molecule, we show that GSNO treatment inhibited proliferation of chemoresponsive and chemoresistant ovarian cancer cell lines (A2780, C200, SKVO3, ID8, OVCAR3, OVCAR4, OVCAR5, OVCAR7, OVCAR8, OVCAR10, PE01 and PE04) in a dose dependent manner. GSNO treatment abrogated growth factor (HB-EGF) induced signal transduction including phosphorylation of Akt, p42/44 and STAT3, which are known to play critical roles in ovarian cancer growth and progression. To examine the therapeutic potential of GSNO in vivo, nude mice bearing intra-peritoneal xenografts of human A2780 ovarian carcinoma cell line (2 × 10(6)) were orally administered GSNO at the dose of 1 mg/kg body weight. Daily oral administration of GSNO significantly attenuated tumor mass (p<0.001) in the peritoneal cavity compared to vehicle (phosphate buffered saline) treated group at 4 weeks. GSNO also potentiated cisplatin mediated tumor toxicity in an A2780 ovarian carcinoma nude mouse model. GSNO's nitrosylating ability was reflected in the induced nitrosylation of various known proteins including NFκB p65, Akt and EGFR. As a novel finding, we observed that GSNO also induced nitrosylation with inverse relationship at tyrosine 705 phosphorylation of STAT3, an established player in chemoresistance and cell proliferation in ovarian cancer and in cancer in general. Overall, our study underlines the significance of S-nitrosylation of key cancer promoting proteins in modulating ovarian cancer and proposes the therapeutic potential of nitrosylating agents (like GSNO) for the treatment of ovarian cancer alone or in combination with chemotherapeutic drugs.
format	article
author	Shailendra Giri Ramandeep Rattan Mandar Deshpande Jacie L Maguire Zachary Johnson Rondell P Graham Viji Shridhar
author_facet	Shailendra Giri Ramandeep Rattan Mandar Deshpande Jacie L Maguire Zachary Johnson Rondell P Graham Viji Shridhar
author_sort	Shailendra Giri
title	Preclinical therapeutic potential of a nitrosylating agent in the treatment of ovarian cancer.
title_short	Preclinical therapeutic potential of a nitrosylating agent in the treatment of ovarian cancer.
title_full	Preclinical therapeutic potential of a nitrosylating agent in the treatment of ovarian cancer.
title_fullStr	Preclinical therapeutic potential of a nitrosylating agent in the treatment of ovarian cancer.
title_full_unstemmed	Preclinical therapeutic potential of a nitrosylating agent in the treatment of ovarian cancer.
title_sort	preclinical therapeutic potential of a nitrosylating agent in the treatment of ovarian cancer.
publisher	Public Library of Science (PLoS)
publishDate	2014
url	https://doaj.org/article/04204642a0234a30a6fe94cde88ff8e4
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Preclinical therapeutic potential of a nitrosylating agent in the treatment of ovarian cancer.

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