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

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. 2018 Apr 24;9(31):21744-21757
Authors: Prasad Tharanga Jayasooriya RG, Dilshara MG, Neelaka Molagoda IM, Park C, Park SR, Lee S, Choi YH, Kim GY
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 thro...

Source: Oncotarget - May 19, 2018 Category: Cancer & Oncology Tags: Oncotarget Source Type: research