Antiproliferative effect of mifepristone (RU486) on human neuroblastoma cells (SK-N-SH): in vitro and in vivo studies
RU486 (mifepristone), a glucocorticoid and progesterone receptor antagonist, has been reported to exert antiproliferative effects on tumor cells. Experiments were performed to analyze the effects of RU486 on the proliferation of the human neuroblastoma, both in vitro and in vivo, using the human neu...
| Main Authors: | , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Associação Brasileira de Divulgação Científica
2020-10-01
|
| Series: | Brazilian Journal of Medical and Biological Research |
| Subjects: | |
| Online Access: | http://www.scielo.br/pdf/bjmbr/v53n11/1414-431X-bjmbr-53-11-e10067.pdf |
| _version_ | 1818365931427987456 |
|---|---|
| author | L.A. Casulari D. Dondi G. Pratesi F. Piva M. Milani M. Piccolella R. Maggi |
| author_facet | L.A. Casulari D. Dondi G. Pratesi F. Piva M. Milani M. Piccolella R. Maggi |
| author_sort | L.A. Casulari |
| collection | DOAJ |
| description | RU486 (mifepristone), a glucocorticoid and progesterone receptor antagonist, has been reported to exert antiproliferative effects on tumor cells. Experiments were performed to analyze the effects of RU486 on the proliferation of the human neuroblastoma, both in vitro and in vivo, using the human neuroblastoma SK-N-SH cell line. The exposure in vitro of SK-N-SH cells to RU486 revealed a dose-dependent inhibition of 3H-thymidine incorporation due to a rapid but persistent inhibition of MAPKinase activity and ERK phosphorylation. A significant decrease of SK-N-SH cell number was evident after 3, 6, and 9 days of treatment (up to 40% inhibition), without evident cell death. The inhibitory effect exerted by RU486 was not reversed by the treatment of the cells with dexamethasone or progesterone. Moreover, RU486 induced a shift in SK-N-SH cell phenotypes, with an almost complete disappearance of the neuronal-like and a prevalence of the epithelial-like cell subtypes. Finally, the treatment with RU486 of nude mice carrying a SK-N-SH cell xenograft induced a strong inhibition (up to 80%) of tumor growth. These results indicated a clear effect of RU486 on the growth of SK-N-SH neuroblastoma cells that does not seem to be mediated through the classical steroid receptors. RU486 acted mainly on the more aggressive component of the SK-N-SH cell line and its effect in vivo was achieved at a concentration already used to inhibit oocyte implantation. |
| first_indexed | 2024-12-13T22:28:06Z |
| format | Article |
| id | doaj.art-13b89f42748645b8918ce54dcbc01f3a |
| institution | Directory Open Access Journal |
| issn | 1414-431X |
| language | English |
| last_indexed | 2024-12-13T22:28:06Z |
| publishDate | 2020-10-01 |
| publisher | Associação Brasileira de Divulgação Científica |
| record_format | Article |
| series | Brazilian Journal of Medical and Biological Research |
| spelling | doaj.art-13b89f42748645b8918ce54dcbc01f3a2022-12-21T23:29:09ZengAssociação Brasileira de Divulgação CientíficaBrazilian Journal of Medical and Biological Research1414-431X2020-10-01531110.1590/1414-431x202010067Antiproliferative effect of mifepristone (RU486) on human neuroblastoma cells (SK-N-SH): in vitro and in vivo studiesL.A. Casularihttps://orcid.org/0000-0002-1315-4127D. DondiG. PratesiF. PivaM. Milanihttps://orcid.org/0000-0001-9525-4131M. Piccolellahttps://orcid.org/0000-0002-5130-1116R. Maggihttps://orcid.org/0000-0002-2733-513XRU486 (mifepristone), a glucocorticoid and progesterone receptor antagonist, has been reported to exert antiproliferative effects on tumor cells. Experiments were performed to analyze the effects of RU486 on the proliferation of the human neuroblastoma, both in vitro and in vivo, using the human neuroblastoma SK-N-SH cell line. The exposure in vitro of SK-N-SH cells to RU486 revealed a dose-dependent inhibition of 3H-thymidine incorporation due to a rapid but persistent inhibition of MAPKinase activity and ERK phosphorylation. A significant decrease of SK-N-SH cell number was evident after 3, 6, and 9 days of treatment (up to 40% inhibition), without evident cell death. The inhibitory effect exerted by RU486 was not reversed by the treatment of the cells with dexamethasone or progesterone. Moreover, RU486 induced a shift in SK-N-SH cell phenotypes, with an almost complete disappearance of the neuronal-like and a prevalence of the epithelial-like cell subtypes. Finally, the treatment with RU486 of nude mice carrying a SK-N-SH cell xenograft induced a strong inhibition (up to 80%) of tumor growth. These results indicated a clear effect of RU486 on the growth of SK-N-SH neuroblastoma cells that does not seem to be mediated through the classical steroid receptors. RU486 acted mainly on the more aggressive component of the SK-N-SH cell line and its effect in vivo was achieved at a concentration already used to inhibit oocyte implantation.http://www.scielo.br/pdf/bjmbr/v53n11/1414-431X-bjmbr-53-11-e10067.pdfMifepristoneRU486Cell proliferationNeuroblastomaNude miceTumor cell growth |
| spellingShingle | L.A. Casulari D. Dondi G. Pratesi F. Piva M. Milani M. Piccolella R. Maggi Antiproliferative effect of mifepristone (RU486) on human neuroblastoma cells (SK-N-SH): in vitro and in vivo studies Brazilian Journal of Medical and Biological Research Mifepristone RU486 Cell proliferation Neuroblastoma Nude mice Tumor cell growth |
| title | Antiproliferative effect of mifepristone (RU486) on human neuroblastoma cells (SK-N-SH): in vitro and in vivo studies |
| title_full | Antiproliferative effect of mifepristone (RU486) on human neuroblastoma cells (SK-N-SH): in vitro and in vivo studies |
| title_fullStr | Antiproliferative effect of mifepristone (RU486) on human neuroblastoma cells (SK-N-SH): in vitro and in vivo studies |
| title_full_unstemmed | Antiproliferative effect of mifepristone (RU486) on human neuroblastoma cells (SK-N-SH): in vitro and in vivo studies |
| title_short | Antiproliferative effect of mifepristone (RU486) on human neuroblastoma cells (SK-N-SH): in vitro and in vivo studies |
| title_sort | antiproliferative effect of mifepristone ru486 on human neuroblastoma cells sk n sh in vitro and in vivo studies |
| topic | Mifepristone RU486 Cell proliferation Neuroblastoma Nude mice Tumor cell growth |
| url | http://www.scielo.br/pdf/bjmbr/v53n11/1414-431X-bjmbr-53-11-e10067.pdf |
| work_keys_str_mv | AT lacasulari antiproliferativeeffectofmifepristoneru486onhumanneuroblastomacellssknshinvitroandinvivostudies AT ddondi antiproliferativeeffectofmifepristoneru486onhumanneuroblastomacellssknshinvitroandinvivostudies AT gpratesi antiproliferativeeffectofmifepristoneru486onhumanneuroblastomacellssknshinvitroandinvivostudies AT fpiva antiproliferativeeffectofmifepristoneru486onhumanneuroblastomacellssknshinvitroandinvivostudies AT mmilani antiproliferativeeffectofmifepristoneru486onhumanneuroblastomacellssknshinvitroandinvivostudies AT mpiccolella antiproliferativeeffectofmifepristoneru486onhumanneuroblastomacellssknshinvitroandinvivostudies AT rmaggi antiproliferativeeffectofmifepristoneru486onhumanneuroblastomacellssknshinvitroandinvivostudies |