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Published on: May 14, 2016
Resveratrol interference with the cell cycle protects human neuroblastoma SH-SY5Y cell from paclitaxel-induced
R Rigolio1, M Miloso, G Nicolini
1Dipartimento di Neuroscienze e Tecnologie Biomediche, Università degli Studi di Milano-Bicocca, Via Cadore 48, 20052 Monza, Italy.
Abstract:
In previous studies we demonstrated that resveratrol acts in an antiapoptotic manner on the paclitaxel-treated human neuroblastoma (HN) SH-SY5Y cell line inhibiting the apoptotic pathways induced by the antineoplastic drug. In the present study we evaluated the antiapoptotic effect of resveratrol, studying its activity on cell cycle progression. We determined the mitotic index of cultures exposed to resveratrol and paclitaxel alone or in combination, the cell cycle distribution by flow cytometric analysis (FACS), and the modulation of some relevant cell cycle regulatory proteins. Resveratrol is able to induce S-phase cell arrest and this interference with the cell cycle is associated with an increase of cyclin E and cyclin A, a downregulation of cyclin D1, and no alteration in cyclin B1 and cdk 1 activation. The resveratrol-induced S-phase block prevents SH-SY5Y from entering into mitosis, the phase of the cell cycle in which paclitaxel exerts its activity, explaining the antiapoptotic effect of resveratrol.
Insights
Resveratrol prevents paclitaxel-induced apoptosis in human neuroblastoma cells by halting the cell cycle at the S-phase. This mechanism explains how resveratrol protects cells from the damaging effects of chemotherapy.
Area of Science:
- Neuroscience
- Cell Biology
- Pharmacology
Background:
- Resveratrol exhibits antiapoptotic properties against paclitaxel in human neuroblastoma (HN) SH-SY5Y cells.
- Previous studies indicated resveratrol inhibits paclitaxel-induced apoptotic pathways.
Purpose of the Study:
- To evaluate the antiapoptotic effect of resveratrol by examining its impact on cell cycle progression.
- To elucidate the molecular mechanisms underlying resveratrol's protective action.
Main Methods:
- Determined mitotic index in cultures treated with resveratrol and paclitaxel.
- Analyzed cell cycle distribution using flow cytometry (FACS).
- Assessed the modulation of key cell cycle regulatory proteins.
Main Results:
- Resveratrol induced an S-phase cell cycle arrest in SH-SY5Y cells.
- This arrest was linked to increased cyclin E and cyclin A, and decreased cyclin D1.
- No alterations were observed in cyclin B1 and cdk 1 activation.
Conclusions:
- Resveratrol's S-phase block prevents cells from entering mitosis, where paclitaxel is most effective.
- This cell cycle interference explains resveratrol's observed antiapoptotic effect against paclitaxel treatment.
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