cDNA microarray analysis of the effect of cantharidin on DNA damage, cell cycle and apoptosis-associated gene expression in NCI-H460 human lung cancer cells in vitro

Hsia,Te‑Chun; Yu,Chien‑Chih; Hsu,Shu‑Chun; Tang,Nou‑Ying; Lu,Hsu‑Feng; Yu,Chun‑Shu; Wu,Shin‑Hwar; Lin,Jaung‑Geng; Chung,Jing‑Gung

doi:10.3892/mmr.2015.3538

July-2015 Volume 12 Issue 1

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July-2015 Volume 12 Issue 1

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Article Open Access

cDNA microarray analysis of the effect of cantharidin on DNA damage, cell cycle and apoptosis-associated gene expression in NCI-H460 human lung cancer cells in vitro

Authors:
- Te‑Chun Hsia
- Chien‑Chih Yu
- Shu‑Chun Hsu
- Nou‑Ying Tang
- Hsu‑Feng Lu
- Chun‑Shu Yu
- Shin‑Hwar Wu
- Jaung‑Geng Lin
- Jing‑Gung Chung
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Affiliations: Graduate Institute of Chinese Medicine, China Medical University, Taichung 40402, Taiwan, R.O.C., School of Pharmacy, China Medical University, Taichung 40402, Taiwan, R.O.C., Department of Biological Science and Technology, China Medical University, Taichung 40402, Taiwan, R.O.C., Department of Clinical Pathology, Cheng Hsin General Hospital, Taipei 11220, Taiwan, R.O.C., Division of Critical Care Medicine, Department of Medicine, Changhua Christian Hospital, Changhua 50006, Taiwan, R.O.C.

Copyright: © Hsia et al. This is an open access article distributed under the terms of Creative Commons Attribution License [CC BY_NC 3.0].
Pages: 1030-1042
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Published online on: March 24, 2015

https://doi.org/10.3892/mmr.2015.3538
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Abstract

Cantharidin (CTD) induces cytotoxic effects in different types of human cancer cell; however, to date, there have been no studies on the effects of CTD on gene expression in human lung cancer cells and the potential associated signaling pathways. Therefore, the present study aimed to investigate how CTD affects the expression of key genes and functional pathways of human H460 lung cancer cells using complementary DNA microarray analysis. Human H460 lung cancer cells were cultured for 24 h in the presence or absence of 10 µM CTD; gene expression was then examined using microarray analysis. The results indicated that 8 genes were upregulated > 4‑fold, 29 genes were upregulated >3‑4‑fold and 156 genes were upregulated >2‑3‑fold. In addition, 1 gene was downregulated >4 fold, 14 genes were downregulated >3‑4‑fold and 150 genes were downregulated >2‑3 fold in H460 cells following exposure to CTD. It was found that CTD affected DNA damage genes, including DNIT3 and GADD45A, which were upregulated 2.26‑ and 2.60‑fold, respectively, as well as DdiT4, which was downregulated 3.14‑fold. In addition, the expression of genes associated with the cell cycle progression were altered, including CCND2, CDKL3 and RASA4, which were upregulated 2.72‑, 2.19‑ and 2.72‑fold, respectively; however, CDC42EP3 was downregulated 2.16‑fold. Furthermore, apoptosis‑associated genes were differentially expressed, including CARD6, which was upregulated 3.54‑fold. In conclusion, the present study demonstrated that CTD affected the expression of genes associated with DNA damage, cell cycle progression and apoptotic cell death in human lung cancer H460 cells.

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1	Bilello KS, Murin S and Matthay RA: Epidemiology, etiology, and prevention of lung cancer. Clin Chest Med. 23:1–25. 2002. View Article : Google Scholar : PubMed/NCBI
2	Parkin DM, Bray F, Ferlay J and Pisani P: Global cancer statistics, 2002. CA Cancer J Clin. 55:74–108. 2005. View Article : Google Scholar : PubMed/NCBI
3	Zhang P, Gao WY, Turner S and Ducatman BS: Gleevec (STI-571) inhibits lung cancer cell growth (A549) and potentiates the cisplatin effect in vitro. Mol Cancer. 2:12003. View Article : Google Scholar : PubMed/NCBI
4	Midthun DE and Jett JR: Chemotherapy for advanced lung cancer. When to expect a response. Postgrad Med. 101:187–194. 1997. View Article : Google Scholar : PubMed/NCBI
5	Stewart DJ: Tumor and host factors that may limit efficacy of chemotherapy in non-small cell and small cell lung cancer. Crit Rev Oncol Hematol. 75:173–234. 2010. View Article : Google Scholar : PubMed/NCBI
6	Chansky K, Sculier JP, Crowley JJ, et al: International Staging Committee and Participating Institutions: The International Association for the Study of Lung Cancer Staging Project: prognostic factors and pathologic TNM stage in surgically managed non-small cell lung cancer. J Thorac Oncol. 4:792–801. 2009. View Article : Google Scholar : PubMed/NCBI
7	Zhang W, Ma YZ, Song L, Wang CH, Qi TG and Shao GR: Effect of cantharidins in chemotherapy for hepatoma: A retrospective cohort study. Am J Chin Med. 42:561–567. 2014. View Article : Google Scholar : PubMed/NCBI
8	Dorn DC, Kou CA, Png KJ and Moore MA: The effect of cantharidins on leukemic stem cells. Int J Cancer. 124:2186–2199. 2009. View Article : Google Scholar : PubMed/NCBI
9	Huh JE, Kang KS, Chae C, Kim HM, Ahn KS and Kim SH: Roles of p38 and JNK mitogen-activated protein kinase pathways during cantharidin-induced apoptosis in U937 cells. Biochem Pharmacol. 67:1811–1818. 2004. View Article : Google Scholar : PubMed/NCBI
10	Li W, Xie L, Chen Z, et al: Cantharidin, a potent and selective PP2A inhibitor, induces an oxidative stress-independent growth inhibition of pancreatic cancer cells through G2/M cell-cycle arrest and apoptosis. Cancer Sci. 101:1226–1233. 2010. View Article : Google Scholar : PubMed/NCBI
11	Yeh CB, Su CJ, Hwang JM and Chou MC: Therapeutic effects of cantharidin analogues without bridging ether oxygen on human hepatocellular carcinoma cells. Eur J Med Chem. 45:3981–3985. 2010. View Article : Google Scholar : PubMed/NCBI
12	Chang C, Zhu YQ, Mei JJ, Liu SQ and Luo J: Involvement of mitochondrial pathway in NCTD-induced cytotoxicity in human hepG2 cells. J Exp Clin Cancer Res. 29:1452010. View Article : Google Scholar : PubMed/NCBI
13	Huang WW, Ko SW, Tsai HY, et al: Cantharidin induces G2/M phase arrest and apoptosis in human colorectal cancer colo 205 cells through inhibition of CDK1 activity and caspase-dependent signaling pathways. Int J Oncol. 38:1067–1073. 2011.PubMed/NCBI
14	Zhang WD, Zhao HR, Yan Y, Wang XH, Zong ZH and Liu Y: Apoptosis induced by cantharidin in human pulmonary carcinoma cells A549 and its molecular mechanisms. Zhonghua Zhong Liu Za Zhi. 27:330–334. 2005.In Chinese. PubMed/NCBI
15	Kim JA, Kim Y, Kwon BM and Han DC: The natural compound cantharidin induces cancer cell death through inhibition of heat shock protein 70 (HSP70) and Bcl-2-associated athanogene domain 3 (BAG3) expression by blocking heat shock factor 1 (HSF1) binding to promoters. J Biol Chem. 288:28713–28726. 2013. View Article : Google Scholar : PubMed/NCBI
16	Osborne C, Wilson P and Tripathy D: Oncogenes and tumor suppressor genes in breast cancer: potential diagnostic and therapeutic applications. Oncologist. 9:361–377. 2004. View Article : Google Scholar : PubMed/NCBI
17	Heneghan HM, Miller N and Kerin MJ: MiRNAs as biomarkers and therapeutic targets in cancer. Curr Opin Pharmacol. 10:543–550. 2010. View Article : Google Scholar : PubMed/NCBI
18	Weinstein IB: Cancer. Addiction to oncogenes – the Achilles heal of cancer. Science. 297:63–64. 2002. View Article : Google Scholar : PubMed/NCBI
19	Luo J, Solimini NL and Elledge SJ: Principles of cancer therapy: oncogene and non-oncogene addiction. Cell. 136:823–837. 2009. View Article : Google Scholar : PubMed/NCBI
20	Solimini NL, Luo J and Elledge SJ: Non-oncogene addiction and the stress phenotype of cancer cells. Cell. 130:986–988. 2007. View Article : Google Scholar : PubMed/NCBI
21	Méndez M, Custodio A and Provencio M: New molecular targeted therapies for advanced non-small cell lung cancer. J Thorac Dis. 3:30–56. 2011.
22	Chang YM, Velmurugan BK, Kuo WW, et al: Inhibitory effect of alpinate Oxyphyllae fructus extracts on Ang II-induced cardiac pathological remodeling-related pathways in H9c2 cardio-myoblast cells. BioMedicine. 3:148–152. 2013. View Article : Google Scholar
23	Hsia TC, Yu CC, Hsu SC, et al: Cantharidin induces apoptosis of H460 human lung cancer cells through mitochondria-dependent pathways. Int J Oncol. 45:245–254. 2014.PubMed/NCBI
24	Ayala F, Dewar R, Kieran M and Kalluri R: Contribution of bone microenvironment to leukemogenesis and leukemia progression. Leukemia. 23:2233–2241. 2009. View Article : Google Scholar : PubMed/NCBI
25	Straussman R, Morikawa T, Shee K, et al: Tumour micro-environment elicits innate resistance to RAF inhibitors through HGF secretion. Nature. 487:500–504. 2012. View Article : Google Scholar : PubMed/NCBI
26	Wilson TR, Fridlyand J, Yan Y, et al: Widespread potential for growth-factor-driven resistance to anticancer kinase inhibitors. Nature. 487:505–509. 2012. View Article : Google Scholar : PubMed/NCBI
27	Moniri MR, Dai LJ and Warnock GL: The challenge of pancreatic cancer therapy and novel treatment strategy using engineered mesenchynmal stem cells. Cancer Gene Ther. 21:12–23. 2014. View Article : Google Scholar : PubMed/NCBI
28	Pignon JP, Tribodet H, Sagliotti GV, et al: LACE Collaborative Group: Lung adjuvant cisplatin evaluation: A pooled analysis by the LACE Collaborative Group. J Clin Oncol. 26:3552–3559. 2008. View Article : Google Scholar : PubMed/NCBI
29	Pepe C, Hasan B, Winton TL, et al National Cancer Institute of Canada and Intergroup Study FBR.10: Adjuvant vinorelbine and cisplatin in elderly patients: National Cancer Institute of Canada and Intergroup Study JBR.10. J Clin Oncol. 25:1553–1561. 2007. View Article : Google Scholar : PubMed/NCBI
30	Glynne-Jones R and Hoskin P: Neoadjuvant cisplatin chemotherapy before chemoradiation: A flawed paradigm? J Clin Oncol. 25:5281–5286. 2007. View Article : Google Scholar : PubMed/NCBI
31	Ricci MS and Zong WX: Chemotherapeutic approaches for targeting cell death pathways. Oncologist. 11:342–357. 2006. View Article : Google Scholar : PubMed/NCBI
32	Tan TT and White E: Therapeutic targeting of death pathways in cancer: Mechanisms for activating cell death in cancer cells. Adv Exp Med Biol. 615:81–104. 2008.PubMed/NCBI