Camptothecin induces G2 /M phase arrest through the ATM-Chk2-Cdc25C axis as a result of autophagy-induced cytoprotection: Implications of reactive oxygen species

Oncotarget
Rajapaksha Gedara Prasad Tharanga JayasooriyaGi-Young Kim

Abstract

In the present study, we report that camptothecin (CPT) caused irreversible cell cycle arrest at the G2/M phase, and was associated with decreased levels of cell division cycle 25C (Cdc25C) and increased levels of cyclin B1, p21, and phospho-H3. Interestingly, the reactive oxygen species (ROS) inhibitor, glutathione, decreased CPT-induced G2/M phase arrest and moderately induced S phase arrest, indicating that the ROS is required for the regulation of CPT-induced G2/M phase arrest. Furthermore, transient knockdown of nuclear factor-erythroid 2-related factor 2 (Nrf2), in the presence of CPT, increased the ROS' level and further shifted the cell cycle from early S phase to the G2/M phase, indicating that Nrf2 delayed the S phase in response to CPT. We also found that CPT-induced G2/M phase arrest increased, along with the ataxia telangiectasia-mutated (ATM)-checkpoint kinase 2 (Chk2)-Cdc25C axis. Additionally, the proteasome inhibitor, MG132, restored the decrease in Cdc25C levels in response to CPT, and significantly downregulated CPT-induced G2/M phase arrest, suggesting that CPT enhances G2/M phase arrest through proteasome-mediated Cdc25C degradation. Our data also indicated that inhibition of extracellular signal-regulated ...Continue Reading

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Citations

Feb 10, 2020·Biomedicine & Pharmacotherapy = Biomédecine & Pharmacothérapie·Chao MeiZhao-Qian Liu
Mar 17, 2021·Food and Chemical Toxicology : an International Journal Published for the British Industrial Biological Research Association·Qingyan RuanGuoyin Kai

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Datasets Mentioned

BETA
U937

Methods Mentioned

BETA
ubiquitination
flow cytometry
nuclear translocation
transfection
environmental stress

Software Mentioned

SigmaPlot
Photoshop
Scion Imaging

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