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Seven Steps to Stellate Cells
Published on: May 10, 2011
Resveratrol inhibits cell growth by inducing cell cycle arrest in activated hepatic stellate cells
Izabel C Souza1, Leo Anderson M Martins, Barbara P Coelho
1Departamento de Bioquímica, Universidade Federal do Rio Grande do Sul, Rua Ramiro Barcelos, 2600-anexo, CEP 90035-003, Porto Alegre, RS, Brazil.
Abstract:
Resveratrol (RSV) exerts anti-proliferative and pro-apoptotic actions in different cell lines. Hepatic stellate cells (HSCs) are major fibrogenic cell types that contribute to collagen accumulation during chronic liver disease. In the present study, the inhibitory effects of RSV on cell proliferation, cell cycle, and apoptosis were evaluated in the mouse hepatic stellate cell line GRX. Cells treated with 1 nM-1 muM of RSV demonstrated a decrease in cell growth of about 35% after 5 days. GRX cells, treated with RSV (100 nM or 1 muM), were analyzed by flow cytometry; RSV induced an increase in the number of GRX cells in the S- and sub-G1 phases. The increase in sub-G1 phase cells and the nuclear condensation and fragmentation shown by DAPI staining identified a possible pro-apoptotic effect of RSV on GRX cells. Furthermore, the RSV anti-proliferative effects could be explained by an S-phase accumulation caused by a decrease in the progression through the cell cycle or an inhibition of S or G2 phase transition. It is notable that these RSV actions are mediated at nanomolar levels, compatible with the concentrations of free RSV in biological fluids after ingestion of polyphenol-rich foods, suggesting a possible effect of these foods as an adjuvant treatment in chronic liver diseases.
Insights
Resveratrol (RSV) significantly inhibits hepatic stellate cell growth and induces apoptosis. These findings suggest polyphenol-rich foods containing RSV may aid in managing chronic liver diseases.
Area of Science:
- Cell Biology
- Biochemistry
- Hepatology
Background:
- Hepatic stellate cells (HSCs) are key fibrogenic cells in chronic liver disease.
- Resveratrol (RSV) exhibits anti-proliferative and pro-apoptotic effects in various cell types.
Purpose of the Study:
- To investigate the inhibitory effects of RSV on the proliferation, cell cycle, and apoptosis of mouse hepatic stellate cells (GRX cell line).
Main Methods:
- GRX cells were treated with varying concentrations of RSV (1 nM–1 μM).
- Cell proliferation was assessed over 5 days.
- Flow cytometry and DAPI staining were used to analyze cell cycle distribution and apoptosis.
Main Results:
- RSV treatment (1 nM–1 μM) reduced GRX cell growth by approximately 35% within 5 days.
- RSV induced accumulation of cells in the S and sub-G1 phases, indicating cell cycle arrest and apoptosis.
- Apoptosis was evidenced by increased sub-G1 phase cells and nuclear fragmentation.
Conclusions:
- RSV demonstrates significant anti-proliferative and pro-apoptotic effects on hepatic stellate cells at nanomolar concentrations.
- These effects may be mediated by S-phase accumulation and cell cycle progression inhibition.
- Dietary intake of RSV-containing foods could potentially serve as an adjuvant therapy for chronic liver diseases.
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