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Published on: May 14, 2016
Girolline, an antitumor compound isolated from a sponge, induces G2/M cell cycle arrest and accumulation of
Sachiko Tsukamoto1, Katsumi Yamashita, Kazuhiro Tane
1Faculty of Pharmaceutical Sciences, Kanazawa University, Japan. sachiko@p.kanazawa-u.ac.jp
Abstract:
Girolline, an antitumor compound isolated from a sponge, has been reported to inhibit the termination step of protein synthesis in vivo. In this study, we found that girolline induced G2/M cell cycle arrest in several tumor cell lines. Immunochemical analysis revealed that polyubiquitinated p53 was accumulated in girolline-treated cells, while other polyubiquitinated cellular proteins were not accumulated, indicating that the effect of girolline is specific for p53. On the other hand, girolline did not inhibit proteasome activity in vitro, and accumulation of polyubiquitinated p53 was scarcely detected in the presence of leptomycin B, an inhibitor of nuclear export. Based on the above findings, we propose that girolline affects the step of recruitment of polyubiquitinated p53 to the proteasome.
Insights
Girolline, an antitumor compound, causes G2/M cell cycle arrest by accumulating p53. This suggests girolline specifically targets the recruitment of polyubiquitinated p53 to the proteasome.
Area of Science:
- Biochemistry
- Molecular Biology
- Pharmacology
Background:
- Girolline is an antitumor compound from a sponge.
- It was previously shown to inhibit protein synthesis termination in vivo.
Purpose of the Study:
- To investigate the mechanism of girolline's antitumor activity.
- To determine the specific cellular targets and pathways affected by girolline.
Main Methods:
- Cell cycle analysis (G2/M arrest) in tumor cell lines.
- Immunochemical analysis of protein ubiquitination and accumulation.
- In vitro proteasome activity assays.
- Experiments using leptomycin B to assess nuclear export inhibition.
Main Results:
- Girolline induced G2/M cell cycle arrest in multiple tumor cell lines.
- Accumulation of polyubiquitinated p53 was observed, but not other polyubiquitinated proteins, indicating specificity for p53.
- Girolline did not inhibit proteasome activity in vitro.
- Reduced p53 accumulation in the presence of leptomycin B suggested a role for nuclear export.
Conclusions:
- Girolline's antitumor effect is linked to specific p53 accumulation.
- The compound appears to interfere with the recruitment of polyubiquitinated p53 to the proteasome, rather than proteasome activity itself.
- Further research into this mechanism could reveal new therapeutic strategies for cancer.
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