Dataset Information

Timosaponin AIII Induces G2/M Arrest and Apoptosis in Breast Cancer by Activating the ATM/Chk2 and p38 MAPK Signaling Pathways.

ABSTRACT: Timosaponin AIII (TAIII), a steroidal saponin, exerts potent anti-tumor activity in various cancers, especially breast cancer. However, the concrete molecular mechanisms of TAIII against breast cancer are still unclear. Here, we find that TAIII triggers DNA damage, leads to G2/M arrest, and ultimately induces apoptosis in breast cancer both in vitro and in vivo. TAIII induced G2/M phase arrest and apoptosis in MDA-MB-231 and MCF7 cells accompanied with down-regulation of CyclinB1, Cdc2 and Cdc25C. Further data showed that the ATM/Chk2 and p38 pathways were activated representing by up-regulated levels of p-H2A.X and p-p38, which indicated an induction of DNA damage by TAIII, leading to cell cycle arrest and apoptosis. The effects of TAIII were further confirmed by employing inhibitors of ATM and p38 pathways. In vivo, TAIII suppressed the growth of subcutaneous xenograft tumor without obvious toxicity, which indicated by Ki67 and TUNEL analysis. Data also showed that TAIII stimulated the ATM/Chk2 and p38 MAPK pathways in vivo, which in consistent with the effects in vitro. Hence, our data demonstrate that TAIII triggers DNA damage and activates ATM/Chk2 and p38 MAPK pathways, and then induces G2/M phase arrest and apoptosis in breast cancer, which provide theoretical evidence for TAIII utilized as drug against breast cancer.

SUBMITTER: Zhang M

PROVIDER: S-EPMC7898553 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Timosaponin AIII Induces G2/M Arrest and Apoptosis in Breast Cancer by Activating the ATM/Chk2 and p38 MAPK Signaling Pathways.

Zhang Minjie M Qu Jiaxi J Gao Zhiwei Z Qi Qi Q Yin Hong H Zhu Ling L Wu Yichen Y Liu Wei W Yang Jian J Huang Xuefeng X

Frontiers in pharmacology 20210115

Timosaponin AIII (TAIII), a steroidal saponin, exerts potent anti-tumor activity in various cancers, especially breast cancer. However, the concrete molecular mechanisms of TAIII against breast cancer are still unclear. Here, we find that TAIII triggers DNA damage, leads to G2/M arrest, and ultimately induces apoptosis in breast cancer both <i>in vitro</i> and <i>in vivo</i>. TAIII induced G2/M phase arrest and apoptosis in MDA-MB-231 and MCF7 cells accompanied with down-regulation of CyclinB1, ...[more]

PMID: 33628174

Similar Datasets

Project description:Vpr is an accessory protein of human immunodeficiency virus type 1 (HIV-1) with multiple functions. The induction of G2 arrest by Vpr plays a particularly important role in efficient viral replication because the transcriptional activity of the HIV-1 long terminal repeat is most active in G2 phase. The regulation of apoptosis by Vpr is also important for immune suppression and pathogenesis during HIV infection. However, it is not known whether Vpr-induced apoptosis depends on the ability of Vpr to induce G2 arrest, and the dynamics of Vpr-induced G2 arrest and apoptosis have not been visualized. We performed time-lapse imaging to examine the temporal relationship between Vpr-induced G2 arrest and apoptosis using HeLa cells containing the fluorescent ubiquitination-based cell cycle indicator2 (Fucci2). The dynamics of G2 arrest and subsequent long-term mitotic cell rounding in cells transfected with the Vpr-expression vector were visualized. These cells underwent nuclear mis-segregation after prolonged mitotic processes and then entered G1 phase. Some cells subsequently displayed evidence of apoptosis after prolonged mitotic processes and nuclear mis-segregation. Interestingly, Vpr-induced apoptosis was seldom observed in S or G2 phase. Likewise, visualization of synchronized HeLa/Fucci2 cells infected with an adenoviral vector expressing Vpr clearly showed that Vpr arrests the cell cycle at G2 phase, but does not induce apoptosis at S or G2 phase. Furthermore, time-lapse imaging of HeLa/Fucci2 cells expressing SCAT3.1, a caspase-3-sensitive fusion protein, clearly demonstrated that Vpr induces caspase-3-dependent apoptosis. Finally, to examine whether the effects of Vpr on G2 arrest and apoptosis were reversible, we performed live-cell imaging of a destabilizing domain fusion Vpr, which enabled rapid stabilization and destabilization by Shield1. The effects of Vpr on G2 arrest and subsequent apoptosis were reversible. This study is the first to characterize the dynamics of the morphological changes that occur during Vpr-induced G2 arrest and apoptosis.

Dataset Information

Timosaponin AIII Induces G2/M Arrest and Apoptosis in Breast Cancer by Activating the ATM/Chk2 and p38 MAPK Signaling Pathways.

Publications

Timosaponin AIII Induces G2/M Arrest and Apoptosis in Breast Cancer by Activating the ATM/Chk2 and p38 MAPK Signaling Pathways.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure