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Updated: Aug 13, 2025
Cell Cycle-specific Measurement of γH2AX and Apoptosis After Genotoxic Stress by Flow Cytometry
Published on: September 1, 2019
The endocytosis inhibitor dynasore induces a DNA damage response pathway that can be manipulated for enhanced
Miki Suemura1, Shusaku Shibutani1, Hiroyuki Iwata1
1Laboratory of Veterinary Hygiene, Joint Faculty of Veterinary Medicine, Yamaguchi University, 1677-1 Yoshida, Yamaguchi, 753-8515, Japan.
Abstract:
Endocytosis has been shown to play an important role in cancer proliferation and metastasis. Recent studies have accumulated evidence that endocytosis inhibitors suppress in vitro and in vivo proliferation and migration. In addition, endocytosis inhibition has been shown to induce apoptosis, but its mechanism remains largely unclear. In this study, we found that the endocytosis inhibitor dynasore causes a cell viability reduction in multiple cancer cell lines, especially in hematopoietic cancers. Dynasore induced massive apoptosis and an S-phase progression delay. In addition, dynasore activated the ATR-Chk1 DNA damage response, which suggests a single-stranded DNA exposure induced by DNA replication stress. Furthermore, an ATR inhibitor sensitized the dynasore-induced apoptosis. These findings suggest that endocytosis inhibitors may have an ability to suppress DNA replication, a common mechanism of genotoxic chemotherapies targeting cancer, and that the anti-cancer effects of endocytosis inhibitors may be sensitized by DNA damage response inhibitors.
Insights
Endocytosis inhibitors like dynasore reduce cancer cell viability and induce apoptosis by causing DNA replication stress. Combining these inhibitors with DNA damage response inhibitors may enhance anti-cancer effects.
Area of Science:
- Oncology
- Molecular Biology
- Cell Biology
Background:
- Endocytosis plays a key role in cancer progression, with inhibitors showing potential against proliferation and metastasis.
- While endocytosis inhibition induces apoptosis, the underlying mechanisms require further elucidation.
Purpose of the Study:
- To investigate the anti-cancer effects and underlying mechanisms of the endocytosis inhibitor dynasore.
- To explore the potential of combining endocytosis inhibitors with DNA damage response inhibitors for cancer therapy.
Main Methods:
- Treatment of multiple cancer cell lines with dynasore.
- Analysis of cell viability, apoptosis, and cell cycle progression.
- Assessment of the DNA damage response pathway activation (ATR-Chk1).
- Evaluation of combination therapy with an ATR inhibitor.
Main Results:
- Dynasore significantly reduced viability and induced apoptosis, particularly in hematopoietic cancers.
- Dynasore caused an S-phase delay, indicating DNA replication stress.
- Dynasore activated the ATR-Chk1 DNA damage response pathway.
- An ATR inhibitor sensitized dynasore-induced apoptosis.
Conclusions:
- Endocytosis inhibition, exemplified by dynasore, can suppress DNA replication, a mechanism shared with genotoxic chemotherapies.
- Endocytosis inhibitors hold promise as anti-cancer agents, with their efficacy potentially enhanced by combination with DNA damage response inhibitors.
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