Effect of progesterone and first evidence about allopregnanolone action on the progression of epithelial human ovarian cancer cell lines

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Ovarian carcinoma is one of the most common cause of death by gynecologic cancer. Several epidemiological and in vitro studies have shown controversial data about progesterone effects in ovarian cancer. Progesterone can be converted in its active metabolite, allopregnanolone, its effects in ovarian...

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Autores principales: Pelegrina, Laura Tatiana, Sanhuesa, María de los Ángeles, Cáceres, Antonella Rosario Ramona, Cuello Carrión, Dario, Rodríguez, Cristina Elisa, Laconi, Myriam Raquel
Formato: Institucional - Material de Difusión
Lenguaje:Inglés
Publicado: Comité editorial Journal of Steroid Biochemistry and Molecular Biology 2020
Materias:
Proliferation
Clonogenic capacity
Migration
Tumorigenic
5α-pregnanes
Acceso en línea:http://repositorio.umaza.edu.ar//handle/00261/1701
https://www.sciencedirect.com/science/article/pii/S0960076019301013?via%3Dihub
Aporte de:
UMAZA Digital (Universidad MAZA - Mendoza) de Universidad Juan Agustín MAZA
id I56-R162-00261-1701
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spelling I56-R162-00261-17012023-07-31T11:17:58Z Effect of progesterone and first evidence about allopregnanolone action on the progression of epithelial human ovarian cancer cell lines Pelegrina, Laura Tatiana Sanhuesa, María de los Ángeles Cáceres, Antonella Rosario Ramona Cuello Carrión, Dario Rodríguez, Cristina Elisa Laconi, Myriam Raquel Proliferation Clonogenic capacity Migration Tumorigenic 5α-pregnanes Ovarian carcinoma is one of the most common cause of death by gynecologic cancer. Several epidemiological and in vitro studies have shown controversial data about progesterone effects in ovarian cancer. Progesterone can be converted in its active metabolite, allopregnanolone, its effects in ovarian cancer are still unknown. Previously, we demonstrated that allopregnanolone modifies ovarian morphophysiology, being able to alter critical process of tumor development such as proliferation, apoptosis and angiogenesis. Taking into account these antecedents, we investigated the effect of progesterone and allopregnanolone on proliferation, apoptosis, clonogenic capacity and migration on two epithelial human ovarian cancer cell lines, IGROV-1 and SKOV-3. To this end, IGROV-1 and SKOV-3 cells were exposed to a range of progesterone and allopregnanolone concentrations (10-11 to 10-5 M) for 72 h. Proliferation was analyzed by MTT and Ki67 expression. Apoptosis was measured by immunocytochemistry of cleaved caspase 3. Clonogenic capacity was evaluated by counting colonies. Migration was analyzed by wound assay. We found that allopregnanolone increased proliferation and Ki67 expression respect to control on IGROV-1 cells, while expression of cleaved caspase 3 did not change in any cell line studied. IGROV-1 clonogenic capacity was also increased by allopregnanolone treatment. Both steroids, progesterone and allopregnanolone, increased IGROV-1 migration in a concentration dependent manner. None of the steroids tested modified SKOV-3 biological behavior analized. This is the first evidence that allopregnanolone, a progesterone metabolite, affects critical events in tumor development of human epithelial ovarian cancer. These results could have an impact in the future in clinic diagnosis, prognosis and treatment of ovarian cancer patients. The regulation of progesterone and allopregnanolone steroideogenesis and their molecular mechanisms might be considered as potential therapeutic tool in ovarian cancer. 2020-08-29T16:45:46Z 2020-08-29T16:45:46Z 2020-02 Institucional - Material de Difusión Pelegrina, L., T., Sanhueza, M. de los A., Cáceres, A. R. R., Cuello Carrion, D., Rodriguez, C. E. y Laconi, M. R. (2020). Effect of progesterone and first evidence about allopregnanolone action on the progression of epithelial human ovarian cancer cell lines. Journal of Steroid Biochemistry and Molecular Biology, 196. Disponible en: https://www.sciencedirect.com/science/article/pii/S0960076019301013?via%3Dihub 0960-0760 http://repositorio.umaza.edu.ar//handle/00261/1701 https://www.sciencedirect.com/science/article/pii/S0960076019301013?via%3Dihub eng image/png Comité editorial Journal of Steroid Biochemistry and Molecular Biology 196;
institution Universidad Juan Agustín MAZA
institution_str I-56
repository_str R-162
collection UMAZA Digital (Universidad MAZA - Mendoza)
language Inglés
orig_language_str_mv eng
topic Proliferation
Clonogenic capacity
Migration
Tumorigenic
5α-pregnanes
spellingShingle Proliferation
Clonogenic capacity
Migration
Tumorigenic
5α-pregnanes
Pelegrina, Laura Tatiana
Sanhuesa, María de los Ángeles
Cáceres, Antonella Rosario Ramona
Cuello Carrión, Dario
Rodríguez, Cristina Elisa
Laconi, Myriam Raquel
Effect of progesterone and first evidence about allopregnanolone action on the progression of epithelial human ovarian cancer cell lines
topic_facet Proliferation
Clonogenic capacity
Migration
Tumorigenic
5α-pregnanes
description Ovarian carcinoma is one of the most common cause of death by gynecologic cancer. Several epidemiological and in vitro studies have shown controversial data about progesterone effects in ovarian cancer. Progesterone can be converted in its active metabolite, allopregnanolone, its effects in ovarian cancer are still unknown. Previously, we demonstrated that allopregnanolone modifies ovarian morphophysiology, being able to alter critical process of tumor development such as proliferation, apoptosis and angiogenesis. Taking into account these antecedents, we investigated the effect of progesterone and allopregnanolone on proliferation, apoptosis, clonogenic capacity and migration on two epithelial human ovarian cancer cell lines, IGROV-1 and SKOV-3. To this end, IGROV-1 and SKOV-3 cells were exposed to a range of progesterone and allopregnanolone concentrations (10-11 to 10-5 M) for 72 h. Proliferation was analyzed by MTT and Ki67 expression. Apoptosis was measured by immunocytochemistry of cleaved caspase 3. Clonogenic capacity was evaluated by counting colonies. Migration was analyzed by wound assay. We found that allopregnanolone increased proliferation and Ki67 expression respect to control on IGROV-1 cells, while expression of cleaved caspase 3 did not change in any cell line studied. IGROV-1 clonogenic capacity was also increased by allopregnanolone treatment. Both steroids, progesterone and allopregnanolone, increased IGROV-1 migration in a concentration dependent manner. None of the steroids tested modified SKOV-3 biological behavior analized. This is the first evidence that allopregnanolone, a progesterone metabolite, affects critical events in tumor development of human epithelial ovarian cancer. These results could have an impact in the future in clinic diagnosis, prognosis and treatment of ovarian cancer patients. The regulation of progesterone and allopregnanolone steroideogenesis and their molecular mechanisms might be considered as potential therapeutic tool in ovarian cancer.
format Institucional - Material de Difusión
author Pelegrina, Laura Tatiana
Sanhuesa, María de los Ángeles
Cáceres, Antonella Rosario Ramona
Cuello Carrión, Dario
Rodríguez, Cristina Elisa
Laconi, Myriam Raquel
author_facet Pelegrina, Laura Tatiana
Sanhuesa, María de los Ángeles
Cáceres, Antonella Rosario Ramona
Cuello Carrión, Dario
Rodríguez, Cristina Elisa
Laconi, Myriam Raquel
author_sort Pelegrina, Laura Tatiana
title Effect of progesterone and first evidence about allopregnanolone action on the progression of epithelial human ovarian cancer cell lines
title_short Effect of progesterone and first evidence about allopregnanolone action on the progression of epithelial human ovarian cancer cell lines
title_full Effect of progesterone and first evidence about allopregnanolone action on the progression of epithelial human ovarian cancer cell lines
title_fullStr Effect of progesterone and first evidence about allopregnanolone action on the progression of epithelial human ovarian cancer cell lines
title_full_unstemmed Effect of progesterone and first evidence about allopregnanolone action on the progression of epithelial human ovarian cancer cell lines
title_sort effect of progesterone and first evidence about allopregnanolone action on the progression of epithelial human ovarian cancer cell lines
publisher Comité editorial Journal of Steroid Biochemistry and Molecular Biology
publishDate 2020
url http://repositorio.umaza.edu.ar//handle/00261/1701
https://www.sciencedirect.com/science/article/pii/S0960076019301013?via%3Dihub
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