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Selective ATP Hydrolysis Inhibition in F1Fo ATP Synthase Enhances Radiosensitivity in Non-Small-Cell Lung Cancer Cells (A549)

Yupei Wang, Qinzheng Hou, Guoqing Xiao, Shifeng Yang, Cuixia Di, Jing Si, Rong Zhou, Yancheng Ye, Yanshan Zhang, Hong Zhang

Oncotarget. 2017 Jun 27;8(32):53602-53612.

PMID: 28881834

Abstract:

Background:
F1Fo-ATP synthase (F1Fo-ATPase) is a reversibly rotary molecular machine whose dual functions of synthesizing or hydrolyzing ATP switch upon the condition of cell physiology. The robust ATP-hydrolyzing activity occurs in ischemia for maintaining the transmembrane proton motive force of mitochondria inner membrane, but the effect of F1Fo-ATPase on X-ray response of non-small-cell lung cancer (NSCLC) cells is unknown.
Methods and findings:
We studied whether ATP hydrolysis affected X-ray radiation induced cell death. NSCLC cells (A549) were pretreated with BTB06584 (BTB), an elective ATP hydrolysis inhibitor, followed by X-ray radiation. Cell viability and clonogenic survival were markedly decreased, clear indications of enhanced radiosensitivity through BTB incubation. Additionally, ATP5α1 was upregulated in parallel with elevated ATP hydrolytic activity after X-ray radiation, showing an increased mitochondrial membrane potential (ΔΨm). ATP hydrolysis inhibition led to collapse of ΔΨm suggesting ATP hydrolytic activity could enhance ΔΨm after X-ray radiation. Furthermore, we also demonstrated that apoptosis was pronounced with the prolonged collapse of ΔΨm due to hydrolysis inhibition by BTB incubation.
Conclusion:
Overall, these findings supported that ATP hydrolysis inhibition could enhance the radiosensitivity in NSCLC cells (A549) after X-ray radiation, which was due to the collapse of ΔΨm.

Chemicals Related in the Paper:

Catalog Number Product Name Structure CAS Number Price
AP219793450 BTB06584 BTB06584 219793-45-0 Price
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