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Lysosomal membrane permeabilization is involved in curcumin-induced apoptosis of A549 lung carcinoma cells

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Abstract

We previously reported that curcumin inhibited lung cancer A549 cells growth and promoted cell apoptosis in vitro. In this study, we further examined the apoptosis-related parameters, including lysosomal damage and cathepsin activation, in A549 cells exposed to curcumin. We found that curcumin caused lysosomal membrane permeabilization (LMP) and cytosolic relocation of cathepsin B (cath B) and cathepsin D (cath D). However, only Z-FA-fmk (a cath B inhibitor) but not pepstatin A (a cath D inhibitor) inhibited curcumin-induced cell apoptosis, mitochondrial membrane potential loss, and cytochrome c release. The antioxidant N-acetylcysteine and glutathione attenuated LMP, suggesting that lysosomal destabilization was dependent on the elevation of reactive oxygen species and which precedes mitochondrial dysfunction. These findings indicated a novel pathway for curcumin regulation of ROS-lysosomal–mitochondrial pathway and provided the key mechanism of regulation of LMP in cell apoptosis, which may be exploited for cancer treatment.

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Abbreviations

JC-1,5,5′,6,6′-tetrachloro-1,1′,3,3′:

Tetraethylbenzi-midazolylcarbocyanineiodide

ROS:

Reactive oxygen species

MMP:

Mitochondrial membrane potential

GSH:

Glutathione

NAC:

N-acetylcysteine

LMP:

Lysosomal membrane permeabilization

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Acknowledgments

This project supported by the Zhejiang Traditional Chinese Medicine Administration Bureau (Project: No. 2008CA077 and No. 2011ZA093) and the Funds of the Nan**g Command Health Speciality “122” Project (Funds: No. 342510001). We would like to thank Drs. Kedi Xu and Yingke Xu for their technical assistance and discussion.

Conflict of interest

All the authors listed have seen the manuscript and approved to submit to your journal. We disclosed no conflicts of interest.

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Authors and Affiliations

  1. Department of Respiratory Disease, The 117th Hospital of PLA, Hang Zhou, 310013, People’s Republic of China

    Qing-Yong Chen, Jian-Guo Shi, De-Min Jiao, Hui-Zhen Hu, Yu-Quan Wu, Jia Song, Jie Yan & Li-Jun Wu

  2. Department of Respiratory Disease, First Affiliated Hospital, Zhejiang Tradition, Medicine University, Hang Zhou, 310003, People’s Republic of China

    Qing-Hua Yao

  3. College of Life Science, Guizhou University, Guiyang, 550025, People’s Republic of China

    Yan-Yi Wang

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  1. Qing-Yong Chen
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Correspondence to Jian-Guo Shi.

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Chen, QY., Shi, JG., Yao, QH. et al. Lysosomal membrane permeabilization is involved in curcumin-induced apoptosis of A549 lung carcinoma cells. Mol Cell Biochem 359, 389–398 (2012). https://doi.org/10.1007/s11010-011-1033-9

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