PMID- 30662813 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20200930 IS - 2156-6976 (Print) IS - 2156-6976 (Electronic) IS - 2156-6976 (Linking) VI - 8 IP - 12 DP - 2018 TI - Incense burning smoke sensitizes lung cancer cells to EGFR TKI by inducing AREG expression. PG - 2575-2589 AB - 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. FAU - Tu, Chih-Yen AU - Tu CY AD - Department of Life Science, National Chung Hsing University Taichung 402, Taiwan. AD - Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, China Medical University Hospital Taichung 404, Taiwan. AD - School of Medicine, China Medical University Taichung 404, Taiwan. FAU - Wang, Bo-Wei AU - Wang BW AD - Graduate Institute of Biomedical Sciences, China Medical University Taichung 404, Taiwan. FAU - Cheng, Fang-Ju AU - Cheng FJ AD - Graduate Institute of Basic Medical Science, China Medical University Taichung 404, Taiwan. FAU - Chen, Chia-Hung AU - Chen CH AD - Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, China Medical University Hospital Taichung 404, Taiwan. AD - School of Medicine, China Medical University Taichung 404, Taiwan. AD - Department of Respiratory Therapy, China Medical University Taichung 404, Taiwan. AD - Graduate Institute of Clinical Medical Science, China Medical University Taichung 404, Taiwan. FAU - Hsia, Te-Chun AU - Hsia TC AD - Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, China Medical University Hospital Taichung 404, Taiwan. AD - Department of Respiratory Therapy, China Medical University Taichung 404, Taiwan. AD - Hyperbaric Oxygen Therapy Center, Department of Internal Medicine, China Medical University Hospital Taichung 404, Taiwan. FAU - Wei, Ya-Ling AU - Wei YL AD - Center for Molecular Medicine, China Medical University and Hospital Taichung 404, Taiwan. FAU - Chen, Chih-Yi AU - Chen CY AD - Department of Surgery, Chang Shan Medical University Taichung, Taiwan. FAU - Hsieh, I-Shan AU - Hsieh IS AD - School of Medicine, China Medical University Taichung 404, Taiwan. AD - Graduate Institute of Biomedical Sciences, China Medical University Taichung 404, Taiwan. FAU - Yeh, Yi-Lun AU - Yeh YL AD - Graduate Institute of Biomedical Sciences, China Medical University Taichung 404, Taiwan. FAU - Wang, Li-Yun AU - Wang LY AD - Graduate Institute of Biomedical Sciences, China Medical University Taichung 404, Taiwan. FAU - Chen, Chuan-Mu AU - Chen CM AD - The iEGG and Animal Biotechnology Center, Ph.D. Program in Translational Medicine, National Chung Hsing University Taichung 402, Taiwan. FAU - Chang, Wei-Chao AU - Chang WC AD - Graduate Institute of Biomedical Sciences, China Medical University Taichung 404, Taiwan. AD - Center for Molecular Medicine, China Medical University and Hospital Taichung 404, Taiwan. AD - The Ph.D. Program for Cancer Biology and Drug Discovery, China Medical University and Academia Sinica Taichung 404, Taiwan. FAU - Huang, Wei-Chien AU - Huang WC AD - Graduate Institute of Biomedical Sciences, China Medical University Taichung 404, Taiwan. AD - Center for Molecular Medicine, China Medical University and Hospital Taichung 404, Taiwan. AD - The Ph.D. Program for Cancer Biology and Drug Discovery, China Medical University and Academia Sinica Taichung 404, Taiwan. AD - Department of Biotechnology, College of Health Science, Asia University Taichung 413, Taiwan. AD - Drug Development Center, China Medical University Taichung, Taiwan. LA - eng PT - Journal Article DEP - 20181201 PL - United States TA - Am J Cancer Res JT - American journal of cancer research JID - 101549944 PMC - PMC6325473 OTO - NOTNLM OT - AREG OT - EGFR OT - Non-small cell lung cancer OT - incent burning smoke COIS- None. EDAT- 2019/01/22 06:00 MHDA- 2019/01/22 06:01 PMCR- 2018/12/01 CRDT- 2019/01/22 06:00 PHST- 2018/02/06 00:00 [received] PHST- 2018/11/13 00:00 [accepted] PHST- 2019/01/22 06:00 [entrez] PHST- 2019/01/22 06:00 [pubmed] PHST- 2019/01/22 06:01 [medline] PHST- 2018/12/01 00:00 [pmc-release] PST - epublish SO - Am J Cancer Res. 2018 Dec 1;8(12):2575-2589. eCollection 2018.