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EnglishOvarian cancer remains the leading cause of mortality among gynecological tumors. Estrogen receptor beta (ERβ) expression has been suggested to act as a tumor suppressor in epithelial ovarian cancer by reducing both tumor growth and metastasis. ERβ expression abnormalities represent a critical step in the development and progression of ovarian cancer: for these reasons, its re‐expression by genetic engineering, as well as the use of targeted ERβ therapies, still constitute an important therapeutic approach. 3‐{[2‐chloro‐1‐(4‐chlorobenzyl)‐5‐methoxy‐6-methyl‐1H‐indol‐3‐yl]methylene}‐5‐hydroxy‐6‐methyl‐1,3‐dihydro‐2H‐indol‐2‐one, referred to here as compound 3, has been shown to have cytostatic as well cytotoxic effects on various hormone-dependent cancer cell lines. However, the mechanism of its anti‐carcinogenic activity is not well understood. Here, we offer a possible explanation of such an effect in the human ovarian cancer cell line IGROV1. Chromatin binding protein assay and liquid chromatography mass spectrometry were exploited to localize and quantify compound 3 in cells. Molecular docking was used to prove compound 3 binding to ERβ. Mass spectrometry‐based approaches were used to analyze histone post‐translational modifications. Finally, gene expression analyses revealed a set of genes regulated by the ERβ/3 complex, namely CCND1, MYC, CDKN2A, and ESR2, providing possible molecular mechanisms that underline the observed antiproliferative effects.
| Titolo: | Indole derivative interacts with estrogen receptor beta and inhibits human ovarian cancer cell growth | |
| Autore/i: | Verardi L.; Fiori J.; Andrisano V.; Locatelli A.; Morigi R.; Naldi M.; Bertucci C.; Strocchi E.; Boga C.; Micheletti G.; Calonghi N. | |
| Autore/i Unibo: | ||
| Anno: | 2020 | |
| Rivista: | ||
| Digital Object Identifier (DOI): | http://dx.doi.org/10.3390/molecules25194438 | |
| Abstract: | Ovarian cancer remains the leading cause of mortality among gynecological tumors. Estrogen receptor beta (ERβ) expression has been suggested to act as a tumor suppressor in epithelial ovarian cancer by reducing both tumor growth and metastasis. ERβ expression abnormalities represent a critical step in the development and progression of ovarian cancer: for these reasons, its re‐expression by genetic engineering, as well as the use of targeted ERβ therapies, still constitute an important therapeutic approach. 3‐{[2‐chloro‐1‐(4‐chlorobenzyl)‐5‐methoxy‐6-methyl‐1H‐indol‐3‐yl]methylene}‐5‐hydroxy‐6‐methyl‐1,3‐dihydro‐2H‐indol‐2‐one, referred to here as compound 3, has been shown to have cytostatic as well cytotoxic effects on various hormone-dependent cancer cell lines. However, the mechanism of its anti‐carcinogenic activity is not well understood. Here, we offer a possible explanation of such an effect in the human ovarian cancer cell line IGROV1. Chromatin binding protein assay and liquid chromatography mass spectrometry were exploited to localize and quantify compound 3 in cells. Molecular docking was used to prove compound 3 binding to ERβ. Mass spectrometry‐based approaches were used to analyze histone post‐translational modifications. Finally, gene expression analyses revealed a set of genes regulated by the ERβ/3 complex, namely CCND1, MYC, CDKN2A, and ESR2, providing possible molecular mechanisms that underline the observed antiproliferative effects. | |
| Data stato definitivo: | 2020-10-14T17:10:12Z | |
| Appare nelle tipologie: | 1.01 Articolo in rivista |
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|---|---|---|---|---|
| molecules-25-04438-v2.pdf | Versione (PDF) editoriale | Licenza per Accesso Aperto. Creative Commons Attribuzione (CCBY) | Open Access Visualizza/Apri |
http://hdl.handle.net/11585/774423
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