Oncotarget

Research Papers:

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 and Hong Zhang _

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Oncotarget. 2017; 8:53602-53612. https://doi.org/10.18632/oncotarget.18657

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Abstract

Yupei Wang1,2,4,5, Qinzheng Hou6, Guoqing Xiao1, Shifeng Yang7, Cuixia Di1,2,4, Jing Si1,2,4, Rong Zhou1,2,4, Yancheng Ye3, Yanshan Zhang3 and Hong Zhang1,2,3,4

1Institute of Modern Physics, Chinese Academy of Sciences, Lanzhou 730000, Gansu, China

2CAS Key Laboratory of Heavy Ion Radiation Biology and Medicine, Institute of Modern Physics, Lanzhou 730000, Gansu, China

3Gansu Wuwei Tumor Hospital, Department of Science and Technology, Wuwei 733000, Gansu, China

4Key Laboratory of Heavy Ion Radiation Medicine of Gansu Province, Institute of Modern Physics, Lanzhou 730000, Gansu, China

5University of Chinese Academy of Sciences, Beijing 100049, China

6College of Life Science, Northwest Normal University, Lanzhou 730070, Gansu, China

7School of Pharmacy, Lanzhou University, Lanzhou 730000, Gansu, China

Correspondence to:

Hong Zhang, email: zhangh@impcas.ac.cn

Keywords: F1Fo-ATP synthase, X-ray radiation, radiosensitivity, mitochondrial membrane potential

Received: March 20, 2017     Accepted: May 23, 2017     Published: June 27, 2017

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.


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