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Graphene-induced apoptosis in lung epithelial cells through EGFR

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Abstract

Expanding interest in nanotechnology applied to electronic and biomedical fields has led to fast-growing development of various nanomaterials. Graphene is a single-atom thick, two-dimensional sheet of hexagonally arranged carbon atoms with unique physical and chemical properties. Recently, graphene has been used in many studies on electronics, photonics, composite materials, energy generation and storage, sensors, and biomedicine. However, the current health risk assessment for graphene has been relatively limited and inconclusive. This study evaluated the toxicity effects of graphene on the airway epithelial cell line BEAS-2B, which represents the first barrier of the human body to interact with airborne graphene particles. Our result showed that graphene can induce the cellular Ca2+ by phospholipase C (PLC) associated pathway by activating epidermal growth factor receptor (EGFR). Subsequently, inositol 1,4,5-triphosphate (IP3) receptors activate the release of Ca2+ from the endoplasmic reticulum (ER) Ca2+ stores. Those Ca2+ signals further trigger the calcium-regulated apoptosis in the cell. Furthermore, the stimulation can cause EGFR upregulation, which have been demonstrated to associate with diseases such as lung cancer, chronic obstructive pulmonary disease (COPD), and cardiovascular diseases. This study highlights the additional health risk considering that it can function as a contributing factor for other respiratory diseases.

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Acknowledgements

The authors thank Mike Dunlap from IMF for the assistance with SEM imaging.

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Author notes

  1. Shih-Ming Tsai and Preeti Bangalore contributed equally

Authors and Affiliations

  1. Bioengineering, University of California at Merced, 5200 North Lake RD, Merced, CA, 95343, USA

    Shih-Ming Tsai, Preeti Bangalore, Eric Y Chen, David Lu, Meng-Hsuen Chiu, Andrew Suh, Matthew Gehring, John P. Cangco, Santiago G. Garcia & Wei-Chun Chin

  2. MicroBase Technology Corp, Bade City, Taoyuan, 33464, Taiwan

    Eric Y Chen

  3. Center for Biomedical Engineering, Chang Gung University, Taoyuan, 33302, Taiwan

    Eric Y Chen

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  1. Shih-Ming Tsai
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  2. Preeti Bangalore
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Contributions

SMT, PB, and EYC: designed the research, conducted the experiments, analyzed and interpreted the data. SMT, PB, MHC, AS, MG, SGG, and WCC: wrote, reviewed, and revised the manuscript. DL and JPC: conducted the experiment. All authors have read and approved the final manuscript.

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Correspondence to Wei-Chun Chin.

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The authors declare that they have no competing interests.

Funding

This study was supported by grants from National Heart, Lung, and Blood Institute (1R15-HL-095039); National Science Foundation (CBET-0932404); and Linkou Chang Gung Memorial Hospital (CMRPG3F0601, CMRPD2F001, and CMRPG3D0082).

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Tsai, SM., Bangalore, P., Chen, E.Y. et al. Graphene-induced apoptosis in lung epithelial cells through EGFR. J Nanopart Res 19, 262 (2017). https://doi.org/10.1007/s11051-017-3957-9

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