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http://dx.doi.org/10.4014/jmb.1712.12009

Benzo[a]pyrene Alters the Expression of Genes in A549 Lung Cancer Cells and Cancer Stem Cells  

Bak, Yesol (Department of Bioscience and Biotechnology, Konkuk University)
Jang, Hui-Joo (Department of Bioscience and Biotechnology, Konkuk University)
Seo, Ji-Hye (Department of Dental Pharmacology, School of Dentistry and Institute of Oral Bioscience, BK21 Plus, Chonbuk National University)
No, Su-Hyun (Department of Dental Pharmacology, School of Dentistry and Institute of Oral Bioscience, BK21 Plus, Chonbuk National University)
Chae, Jung-il (Department of Dental Pharmacology, School of Dentistry and Institute of Oral Bioscience, BK21 Plus, Chonbuk National University)
Hong, Jintae (College of Pharmacy and Medical Research Center, Chungbuk National University)
Yoon, Do-Young (Department of Bioscience and Biotechnology, Konkuk University)
Publication Information
Journal of Microbiology and Biotechnology / v.28, no.3, 2018 , pp. 425-431 More about this Journal
Abstract
Benzo[a]pyrene (B[a]P), a polycyclic aromatic hydrocarbon, is a principal component of cigarette smoke. B[a]P can cause lung carcinogenesis and plays a key role in lung cancer progression. The role of B[a]P has been reported in lung cancer, but its effects on lung cancer stem cells (CSCs) have not been investigated. Emerging evidence indicates that CSCs are associated with carcinogenesis, tumor initiation, relapse, and metastasis. Therefore, targeting CSCs to defeat cancer is a challenging issue in the clinic. This study explored whether B[a]P alters gene expression in lung cancer cells and CSCs. The lung adenocarcinoma A549 cell line was used to investigate the role of B[a]P on lung cancer cells and lung CSCs using microarray and quantitative PCR. B[a]P ($1{\mu}M$) provoked gene expression changes in A549 cancer cells and CSCs by deregulating numerous genes. Gene pathway analysis was performed using GeneMANIA and GIANT. We identified genes that were coexpressed and showed physical interactions. These findings improve our understanding of the mechanism of B[a]P in lung cancer and cancer stem cells and can be an attractive therapeutic target.
Keywords
Microarray; quantitative PCR; lung cancer; cancer stem cell; benzo[a]pyrene;
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1 Torre LA, Bray F, Siegel RL, Ferlay J, Lortet-Tieulent J, Jemal A. 2015. Global cancer statistics, 2012. CA Cancer J. Clin. 65: 87-108.   DOI
2 Parkin DM, Bray F, Ferlay J, Pisani P. 2001. Estimating the world cancer burden: Globocan 2000. Int. J. Cancer 94: 153-156.   DOI
3 DeSantis CE, Lin CC, Mariotto AB, Siegel RL, Stein KD, Kramer JL, et al. 2014. Cancer treatment and survivorship statistics, 2014. CA Cancer J. Clin. 64: 252-271.   DOI
4 Uramoto H, Tanaka F. 2014. Recurrence after surgery in patients with NSCLC. Trans. Lung Cancer Res. 3: 242-249.
5 Dick JE. 2008. Stem cell concepts renew cancer research. Blood 112: 4793-4807.   DOI
6 Reya T, Morrison SJ, Clarke MF, Weissman IL. 2001. Stem cells, cancer, and cancer stem cells. Nature 414: 105-111.   DOI
7 Freedman ND, Leitzmann MF, Hollenbeck AR, Schatzkin A, Abnet CC. 2008. Cigarette smoking and subsequent risk of lung cancer in men and women: analysis of a prospective cohort study. Lancet Oncol. 9: 649-656.   DOI
8 Kalabus JL, Cheng Q, Jamil RG, Schuetz EG, Blanco JG. 2012. Induction of carbonyl reductase 1 (CBR1) expression in human lung tissues and lung cancer cells by the cigarette smoke constituent benzo[a]pyrene. Toxicol. Lett. 211: 266-273.   DOI
9 Wang Y, Jia Y, Yan L, Fu J, Hao M, Chen W, et al. 2017. Clusterin and neuropilin-2 as potential biomarkers of tumor progression in benzo[a]pyrene-transformed 16HBE cells xenografted nude mouse model. Chem. Biol. Interact. 275: 145-151.   DOI
10 Bak Y, Kwon T, Bak IS, Hong J, Yu DY, Yoon DY. 2016. IL-32theta inhibits stemness and epithelial-mesenchymal transition of cancer stem cells via the STAT3 pathway in colon cancer. Oncotarget 7: 7307-7317.
11 Kakarala M, Wicha MS. 2008. Implications of the cancer stem-cell hypothesis for breast cancer prevention and therapy. J. Clin. Oncol. 26: 2813-2820.   DOI
12 Chen X, Peng H, Xiao J, Guan A, Xie B, He B, et al. 2017. Benzo(a)pyrene enhances the EMT-associated migration of lung adenocarcinoma A549 cells by upregulating Twist1. Oncol. Rep. 38: 2141-2147.   DOI
13 Pastrana E, Silva-Vargas V, Doetsch F. 2011. Eyes wide open: a critical review of sphere-formation as an assay for stem cells. Cell Stem Cell 8: 486-498.   DOI
14 Zheng H, Kang Y. 2014. Multilayer control of the EMT master regulators. Oncogene 33: 1755-1763.   DOI
15 Cai Y, Kleiner H, Johnston D, Dubowski A, Bostic S, Ivie W, et al. 1997. Effect of naturally occurring coumarins on the formation of epidermal DNA adducts and skin tumors induced by benzo[a]pyrene and 7,12-dimethylbenz[a]anthracene in SENCAR mice. Carcinogenesis 18: 1521-1527.   DOI
16 Kasala ER, Bodduluru LN, Barua CC, Gogoi R. 2016. Antioxidant and antitumor efficacy of luteolin, a dietary flavone on benzo(a)pyrene-induced experimental lung carcinogenesis. Biomed. Pharmacother. 82: 568-577.
17 Park SY, Lee SM, Ye SK, Yoon SH, Chung MH, Choi J. 2006. Benzo[a]pyrene-induced DNA damage and p53 modulation in human hepatoma HepG2 cells for the identification of potential biomarkers for PAH monitoring and risk assessment. Toxicol. Lett. 167: 27-33.
18 Rathore K, Wang HC. 2013. Mesenchymal and stem-like cell properties targeted in suppression of chronically-induced breast cell carcinogenesis. Cancer Lett. 333: 113-123.
19 Levi E, Misra S, Du J, Patel BB, Majumdar AP. 2009. Combination of aging and dimethylhydrazine treatment causes an increase in cancer-stem cell population of rat colonic crypts. Biochem. Biophys. Res. Commun. 385: 430-433.   DOI
20 Kim H, Yang XL, Rosada C, Hamilton SR, August JT. 1994. CD44 expression in colorectal adenomas is an early event occurring prior to K-ras and p53 gene mutation. Arch. Biochem. Biophys. 310: 504-507.   DOI
21 Pei XH, Nakanishi Y, Takayama K, Bai F, Hara N. 1999. Benzo[a]pyrene activates the human p53 gene through induction of nuclear factor kappaB activity. J. Biol. Chem. 274: 35240-35246.   DOI