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Anti-proliferative effect of LXR agonist T0901317 in ovarian carcinoma cells
BACKGROUND: Ovarian cancer is the most common cause of cancer related death from gynecologic tumors in the United States. The insidious nature of the disease precludes early diagnosis, therefore surgical debulking and chemotherapy are considered as standard treatment modalities for advanced stages....
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Formato: | Texto |
Lenguaje: | English |
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BioMed Central
2010
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2890636/ https://www.ncbi.nlm.nih.gov/pubmed/20504359 http://dx.doi.org/10.1186/1757-2215-3-13 |
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author | Rough, James J Monroy, M Alexandra Yerrum, Smitha Daly, John M |
author_facet | Rough, James J Monroy, M Alexandra Yerrum, Smitha Daly, John M |
author_sort | Rough, James J |
collection | PubMed |
description | BACKGROUND: Ovarian cancer is the most common cause of cancer related death from gynecologic tumors in the United States. The insidious nature of the disease precludes early diagnosis, therefore surgical debulking and chemotherapy are considered as standard treatment modalities for advanced stages. We investigated the effect of the LXR agonist, T0901317, on ovarian cancer cell proliferation and apoptosis as a potential therapeutic agent. RESULTS: T0901317 treatment resulted in a significant (P <0.001) inhibition of cell proliferation in a time- and dose-dependent manner in CaOV3, SKOV3 and A2780 cells. Western blot analysis demonstrated an induction of p21 and p27 with a concominant reduction in phospho-RB protein levels. Cell cycle analysis demonstrated a significant (P <0.001) arrest in the G1 cell cycle phase. Significant induction of Caspase-3 and BAX gene expression occurred with treatment. Induction of apoptosis was confirmed by significant (P < 0.001) elevation of caspase activity on FACS analysis, caspase-glo assay, BAX protein induction and decreased caspase 3 precursor protein expression on Western blot analysis. LXR α/β knockdown experiments did not reverse the anti-proliferative and cytotoxic effects of T0901317. CONCLUSIONS: The LXR agonist, T0901317, significantly suppresses cell proliferation and induces programmed cell death in a dose- and time-dependent manner. Our results indicate that T0901317 induces its anti-proliferative and cytotoxic effects via an LXR-independent mechanism. |
format | Text |
id | pubmed-2890636 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2010 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-28906362010-06-24 Anti-proliferative effect of LXR agonist T0901317 in ovarian carcinoma cells Rough, James J Monroy, M Alexandra Yerrum, Smitha Daly, John M J Ovarian Res Research BACKGROUND: Ovarian cancer is the most common cause of cancer related death from gynecologic tumors in the United States. The insidious nature of the disease precludes early diagnosis, therefore surgical debulking and chemotherapy are considered as standard treatment modalities for advanced stages. We investigated the effect of the LXR agonist, T0901317, on ovarian cancer cell proliferation and apoptosis as a potential therapeutic agent. RESULTS: T0901317 treatment resulted in a significant (P <0.001) inhibition of cell proliferation in a time- and dose-dependent manner in CaOV3, SKOV3 and A2780 cells. Western blot analysis demonstrated an induction of p21 and p27 with a concominant reduction in phospho-RB protein levels. Cell cycle analysis demonstrated a significant (P <0.001) arrest in the G1 cell cycle phase. Significant induction of Caspase-3 and BAX gene expression occurred with treatment. Induction of apoptosis was confirmed by significant (P < 0.001) elevation of caspase activity on FACS analysis, caspase-glo assay, BAX protein induction and decreased caspase 3 precursor protein expression on Western blot analysis. LXR α/β knockdown experiments did not reverse the anti-proliferative and cytotoxic effects of T0901317. CONCLUSIONS: The LXR agonist, T0901317, significantly suppresses cell proliferation and induces programmed cell death in a dose- and time-dependent manner. Our results indicate that T0901317 induces its anti-proliferative and cytotoxic effects via an LXR-independent mechanism. BioMed Central 2010-05-26 /pmc/articles/PMC2890636/ /pubmed/20504359 http://dx.doi.org/10.1186/1757-2215-3-13 Text en Copyright ©2010 Rough et al; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Research Rough, James J Monroy, M Alexandra Yerrum, Smitha Daly, John M Anti-proliferative effect of LXR agonist T0901317 in ovarian carcinoma cells |
title | Anti-proliferative effect of LXR agonist T0901317 in ovarian carcinoma cells |
title_full | Anti-proliferative effect of LXR agonist T0901317 in ovarian carcinoma cells |
title_fullStr | Anti-proliferative effect of LXR agonist T0901317 in ovarian carcinoma cells |
title_full_unstemmed | Anti-proliferative effect of LXR agonist T0901317 in ovarian carcinoma cells |
title_short | Anti-proliferative effect of LXR agonist T0901317 in ovarian carcinoma cells |
title_sort | anti-proliferative effect of lxr agonist t0901317 in ovarian carcinoma cells |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2890636/ https://www.ncbi.nlm.nih.gov/pubmed/20504359 http://dx.doi.org/10.1186/1757-2215-3-13 |
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