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Published on: September 13, 2018
Abemaciclib induces apoptosis in cardiomyocytes by activating the Hippo signaling pathway
Yajie Zhou1,2, Yanfei Li3, Junwei Shen4
1Clinical Medical College, Guizhou Medical University, Guiyang 550004, China.
Insights
Abemaciclib, a new breast cancer drug, may harm heart cells by triggering apoptosis and inhibiting proliferation via the Hippo pathway. This research reveals the molecular mechanism behind potential cardiac side effects.
Area of Science:
- Cardiology
- Oncology
- Molecular Biology
Background:
- Abemaciclib is an FDA-approved cyclin-dependent kinase 4/6 inhibitor for advanced breast cancer.
- Potential adverse effects on cardiomyocytes are not well understood.
Purpose of the Study:
- To investigate the effects of abemaciclib on human cardiomyocyte cells.
- To elucidate the molecular mechanisms underlying abemaciclib-induced cardiotoxicity.
Main Methods:
- Cell counting kit-8 assay
- Western blot analysis
- Flow cytometry
- Immunostaining
- Quantitative polymerase chain reaction (qPCR) on AC16 human cardiomyocyte cells.
Main Results:
- Abemaciclib significantly inhibited viability and proliferation of AC16 cells.
- Abemaciclib induced apoptosis in AC16 cells.
- Activation of the Hippo signaling pathway was observed.
Conclusions:
- Abemaciclib induces cardiomyocyte apoptosis and inhibits proliferation through Hippo pathway activation.
- This study provides insights into the molecular basis of abemaciclib's cardiac side effects.
- Identifies potential therapeutic targets for managing cardiotoxicity.
Abstract:
Abemaciclib is the newest cyclin-dependent kinase 4/6 inhibitor that has received approval from the US Food and Drug Administration for using in patients with advanced breast cancer. However, its potential adverse effects on cardiomyocytes remain unknown. In this study, we used the cell counting kit-8 assay, western blot analysis, flow cytometry, immunostaining, and quantitative polymerase chain reaction to investigate the role of abemaciclib in inducing apoptosis and in inhibiting the viability and proliferation of AC16 human cardiomyocyte cells. The results revealed that abemaciclib induced apoptosis and inhibited cell proliferation by activating the Hippo signaling pathway. This work demonstrates the molecular basis by which abemaciclib induces cardiac side effects, providing a theoretical basis and effective targets for the treatment of cardiac diseases.
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