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Am J Cancer Res. 2018 Dec 1;8(12):2575-2589. eCollection 2018.

Incense burning smoke sensitizes lung cancer cells to EGFR TKI by inducing AREG expression.

Tu CY1,2,3, Wang BW4, Cheng FJ5, Chen CH2,3,6,7, Hsia TC2,6,8, Wei YL9, Chen CY10, Hsieh IS3,4, Yeh YL4, Wang LY4, Chen CM11, Chang WC4,9,12, Huang WC4,9,12,13,14.

Author information

1
Department of Life Science, National Chung Hsing University Taichung 402, Taiwan.
2
Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, China Medical University Hospital Taichung 404, Taiwan.
3
School of Medicine, China Medical University Taichung 404, Taiwan.
4
Graduate Institute of Biomedical Sciences, China Medical University Taichung 404, Taiwan.
5
Graduate Institute of Basic Medical Science, China Medical University Taichung 404, Taiwan.
6
Department of Respiratory Therapy, China Medical University Taichung 404, Taiwan.
7
Graduate Institute of Clinical Medical Science, China Medical University Taichung 404, Taiwan.
8
Hyperbaric Oxygen Therapy Center, Department of Internal Medicine, China Medical University Hospital Taichung 404, Taiwan.
9
Center for Molecular Medicine, China Medical University and Hospital Taichung 404, Taiwan.
10
Department of Surgery, Chang Shan Medical University Taichung, Taiwan.
11
The iEGG and Animal Biotechnology Center, Ph.D. Program in Translational Medicine, National Chung Hsing University Taichung 402, Taiwan.
12
The Ph.D. Program for Cancer Biology and Drug Discovery, China Medical University and Academia Sinica Taichung 404, Taiwan.
13
Department of Biotechnology, College of Health Science, Asia University Taichung 413, Taiwan.
14
Drug Development Center, China Medical University Taichung, Taiwan.

Abstract

Incense burning is common in Asian countries due to the religious beliefs. Environmental exposure to incense burning smoke is a potential risk factor for tumor development and progression of non-small cell lung cancer (NSCLC). Eastern Asia ethnic origin is strongly associated the clinical benefits of epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) in NSCLC patients. However, the impact of the oriental custom of incense burning on the cancer progression and the EGFR TKI-sensitivity of NSCLC remains unclear. Our results showed that long-term exposure to incense burning extract (IBE) increases the cellular proliferation with S phase accumulation and the motility activity of NSCLCs. Interestingly, IBE enhances EGFR signaling activity without affecting its genetic status, and increases the cellular sensitivity of NSCLC cell lines to EGFR TKIs. Auramine, a yellow dye for making incense sticks, was identified as a residual composition in the burning incense smoke, and showed similar EGFR TKI-sensitizing effects. Furthermore, IBE or auramine transcriptionally induce EGFR ligand amphiregulin (AREG) expression for the enhancement of EGFR activity. Neutralization of AREG reduced the viability of IBE-treated cells. These results indicated that exposure to incent smoke may enhance NSCLC progression and their sensitivity to EGFR TKIs through increasing their oncogenic addiction to AREG-induced EGFR signaling.

KEYWORDS:

AREG; EGFR; Non-small cell lung cancer; incent burning smoke

PMID:
30662813
PMCID:
PMC6325473

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