Resveratrol-induced cellular apoptosis and cell cycle arrest in neuroblastoma cells and antitumor effects on neuroblastoma in mice
Journal
Surgery
Journal Volume
136
Journal Issue
1
Pages
57-66
Date Issued
2004
Author(s)
Abstract
Background The prognosis of neuroblastoma patients remains unsatisfactory. Therefore, developing an effective treatment strategy is important. Resveratrol, a natural polyphenol, possesses chemopreventive and antitumor effects. We investigated the effects of resveratrol on the proliferation, apoptosis, and cell cycle alteration of neuroblastoma cells and determined its effects on neuroblastoma tumors in mice. Methods Cytotoxic effects, cellular apoptosis, and alterations in the cell cycle were determined in neuro-2a neuroblastoma cells exposed for varying lengths of time to a series of resveratrol concentrations. Expression of associated cell cycle regulatory proteins, cyclin E and p21, was detected by Western blot analysis, and the antitumor effects of resveratrol were investigated by treating subcutaneous neuroblastoma tumors with intraperitoneal injections of 40 mg/kg resveratrol daily for 28 days. Results Resveratrol exerted cytotoxic effects on neuroblastoma cells. After resveratrol treatment, the apoptosis rate of the neuroblastoma cells significantly increased, a significant accumulation of cells occurred at the S phase of the cell cycle, p21 was downregulated, and cyclin E was upregulated. In addition, resveratrol treatment suppressed the growth rate of subcutaneous neuroblastomas, resulting in 70% long-term survival. Conclusion Resveratrol caused significant cytotoxicity and increased apoptosis and S-phase accumulation of neuroblastoma cells. S-phase accumulation was related to the down-regulation of p21 and up-regulation of cyclin E. In addition, resveratrol exerted antitumor effects on neuroblastomas in mice. Thus, resveratrol shows promise for the treatment of neuroblastoma.
SDGs
Other Subjects
caspase 3 inhibitor; cyclin E; protein p21; regulator protein; resveratrol; animal cell; animal experiment; animal model; animal tissue; antineoplastic activity; apoptosis; article; cancer inhibition; cancer survival; cell cycle; cell cycle S phase; cell proliferation; controlled study; cytotoxicity; down regulation; drug effect; male; mitosis inhibition; mouse; neuroblastoma; neuroblastoma cell; nonhuman; priority journal; protein expression; survival time; tumor growth; upregulation; Western blotting; Animals; Antineoplastic Agents, Phytogenic; Apoptosis; Cell Cycle; Cell Line, Tumor; Mice; Neuroblastoma; Stilbenes
Type
journal article