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Article

Reduced apurinic/apyrimidinic endonuclease activity enhances the antitumor activity of oxymatrine in lung cancer cells

  • Authors:
    • Zhiqiang Wang
    • Wenya Xu
    • Ziying Lin
    • Chunyan Li
    • Yahong Wang
    • Lawei Yang
    • Gang Liu
  • View Affiliations / Copyright

    Affiliations: Clinical Research Center, Affiliated Hospital of Guangdong Medical University, Zhanjiang, Guangdong 524001, P.R. China
  • Pages: 2331-2340
    |
    Published online on: October 14, 2016
       https://doi.org/10.3892/ijo.2016.3734
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Abstract

Lung cancer is the leading cause of cancer-related deaths worldwide and is associated with a very poor outcome. Oxymatrine exerts antitumor effects by inducing apoptosis and inhibiting the proliferation of different cancer cells; however, the anticancer effects and mechanism of action of oxymatrine have not been evaluated sufficiently in human lung cancer cells. Thus, the present study aimed to investigate the anticancer effects of oxymatrine in human lung cancer cells and identify the molecular mechanisms underlying these effects. MTT assays demonstrated that oxymatrine significantly inhibited the proliferation of A549 and H1299 cells in a time- and dose-dependent manner. In addition, flow cytometry and terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end-labeling assays suggested that oxymatrine treatment may induce lung cancer cell apoptosis in a dose-dependent manner. Furthermore, we detected that oxymatrine induced a significant increase in DNA damage and the expression of PARP and phosphorylated H2AX, and a significant decrease in that of nuclear APE1 and AP endonuclease activity in A549 cells. APE1 knockdown cells (APE1shRNA) plus oxymatrine treatment reduced cells proliferation and induced apoptosis more seriously than control shRNA cells. This appeared to be a consequence of an increase in the number of apurinic/apyrimidinic (AP) sites, DNA damage, PARP and H2AX phosphorylation, which together resulted in the induction of apoptosis. In contrast, the sensitizing effects of APE1 overexpression plus oxymatrine treatment did not occur in APEOE cells. These findings reveal a potential mechanism of action for oxymatrine-induced apoptosis and suggest that oxymatrine is a promising potential therapeutic agent for the treatment of lung cancer.
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1 

Dasari S and Tchounwou PB: Cisplatin in cancer therapy: Molecular mechanisms of action. Eur J Pharmacol. 740:364–378. 2014. View Article : Google Scholar : PubMed/NCBI

2 

Liu YH, Li ML, Hsu MY, Pang YY, Chen IL, Chen CK, Tang SW, Lin HY and Lin JY: Effects of a Chinese herbal medicine, Guan-Jen-Huang (Aeginetia indica Linn.), on renal cancer cell growth and metastasis. Evid Based Complement Alternat Med. 2012:9358602012. View Article : Google Scholar

3 

Huang M, Hu YY, Dong XQ, Xu QP, Yu WH and Zhang ZY: The protective role of oxymatrine on neuronal cell apoptosis in the hemorrhagic rat brain. J Ethnopharmacol. 143:228–235. 2012. View Article : Google Scholar : PubMed/NCBI

4 

Chai NL, Fu Q, Shi H, Cai CH, Wan J, Xu SP and Wu BY: Oxymatrine liposome attenuates hepatic fibrosis via targeting hepatic stellate cells. World J Gastroenterol. 18:4199–4206. 2012. View Article : Google Scholar : PubMed/NCBI

5 

Hong-Li S, Lei L, Lei S, Dan Z, De-Li D, Guo-Fen Q, Yan L, Wen-Feng C and Bao-Feng Y: Cardioprotective effects and underlying mechanisms of oxymatrine against ischemic myocardial injuries of rats. Phytother Res. 22:985–989. 2008. View Article : Google Scholar : PubMed/NCBI

6 

Ling Q, Xu X, Wei X, Wang W, Zhou B, Wang B and Zheng S: Oxymatrine induces human pancreatic cancer PANC-1 cells apoptosis via regulating expression of Bcl-2 and IAP families, and releasing of cytochrome c. J Exp Clin Cancer Res. 30:662011. View Article : Google Scholar : PubMed/NCBI

7 

Liu Y, Xu Y, Ji W, Li X, Sun B, Gao Q and Su C: Anti-tumor activities of matrine and oxymatrine: Literature review. Tumour Biol. 35:5111–5119. 2014. View Article : Google Scholar : PubMed/NCBI

8 

Song G, Luo Q, Qin J, Wang L, Shi Y and Sun C: Effects of oxymatrine on proliferation and apoptosis in human hepatoma cells. Colloids Surf B Biointerfaces. 48:1–5. 2006. View Article : Google Scholar : PubMed/NCBI

9 

Wang D, Xiang DB, Yang XQ, Chen LS, Li MX, Zhong ZY and Zhang YS: APE1 overexpression is associated with cisplatin resistance in non-small cell lung cancer and targeted inhibition of APE1 enhances the activity of cisplatin in A549 cells. Lung Cancer. 66:298–304. 2009. View Article : Google Scholar : PubMed/NCBI

10 

Helleday T, Petermann E, Lundin C, Hodgson B and Sharma RA: DNA repair pathways as targets for cancer therapy. Nat Rev Cancer. 8:193–204. 2008. View Article : Google Scholar : PubMed/NCBI

11 

Kelley MR, Georgiadis MM and Fishel ML: APE1/Ref-1 role in redox signaling: Translational applications of targeting the redox function of the DNA repair/redox protein APE1/Ref-1. Curr Mol Pharmacol. 5:36–53. 2012. View Article : Google Scholar :

12 

Xanthoudakis S, Smeyne RJ, Wallace JD and Curran T: The redox/DNA repair protein, Ref-1, is essential for early embryonic development in mice. Proc Natl Acad Sci USA. 93:8919–8923. 1996. View Article : Google Scholar : PubMed/NCBI

13 

Lindahl T: Instability and decay of the primary structure of DNA. Nature. 362:709–715. 1993. View Article : Google Scholar : PubMed/NCBI

14 

Dianov GL, Sleeth KM, Dianova II and Allinson SL: Repair of abasic sites in DNA. Mutat Res. 531:157–163. 2003. View Article : Google Scholar : PubMed/NCBI

15 

Bapat A, Glass LS, Luo M, Fishel ML, Long EC, Georgiadis MM and Kelley MR: Novel small-molecule inhibitor of apurinic/apyrimidinic endonuclease 1 blocks proliferation and reduces viability of glioblastoma cells. J Pharmacol Exp Ther. 334:988–998. 2010. View Article : Google Scholar : PubMed/NCBI

16 

Wu C, Huang W, Guo Y, Xia P, Sun X, Pan X and Hu W: Oxymatrine inhibits the proliferation of prostate cancer cells in vitro and in vivo. Mol Med Rep. 11:4129–4134. 2015.PubMed/NCBI

17 

Wei J, Zhu Y, Xu G, Yang F, Guan Z, Wang M and Fang Y: Oxymatrine extracted from Sophora flavescens inhibited cell growth and induced apoptosis in human osteosarcoma MG-63 cells in vitro. Cell Biochem Biophys. 70:1439–1444. 2014. View Article : Google Scholar : PubMed/NCBI

18 

Wang L, Hou X, Fu H, Pan X, Xu W, Tang W and Fang H: Design, synthesis and preliminary bioactivity evaluations of substituted quinoline hydroxamic acid derivatives as novel histone deacetylase (HDAC) inhibitors. Bioorg Med Chem. 23:4364–4374. 2015. View Article : Google Scholar : PubMed/NCBI

19 

Valdiglesias V, Giunta S, Fenech M, Neri M and Bonassi S: γH2AX as a marker of DNA double strand breaks and genomic instability in human population studies. Mutat Res. 753:24–40. 2013. View Article : Google Scholar : PubMed/NCBI

20 

Schreiber V, Dantzer F, Ame JC and de Murcia G: Poly(ADP-ribose): Novel functions for an old molecule. Nat Rev Mol Cell Biol. 7:517–528. 2006. View Article : Google Scholar : PubMed/NCBI

21 

Muñoz-Gámez JA, Rodríguez-Vargas JM, Quiles-Pérez R, Aguilar-Quesada R, Martín-Oliva D, de Murcia G, Menissier de Murcia J, Almendros A, Ruiz de Almodóvar M and Oliver FJ: PARP-1 is involved in autophagy induced by DNA damage. Autophagy. 5:61–74. 2009. View Article : Google Scholar

22 

Krishnakumar R and Kraus WL: The PARP side of the nucleus: Molecular actions, physiological outcomes, and clinical targets. Mol Cell. 39:8–24. 2010. View Article : Google Scholar : PubMed/NCBI

23 

Scott TL, Rangaswamy S, Wicker CA and Izumi T: Repair of oxidative DNA damage and cancer: Recent progress in DNA base excision repair. Antioxid Redox Signal. 20:708–726. 2014. View Article : Google Scholar :

24 

Evans AR, Limp-Foster M and Kelley MR: Going APE over ref-1. Mutat Res. 461:83–108. 2000. View Article : Google Scholar : PubMed/NCBI

25 

Madhusudan S, Smart F, Shrimpton P, Parsons JL, Gardiner L, Houlbrook S, Talbot DC, Hammonds T, Freemont PA, Sternberg MJ, et al: Isolation of a small molecule inhibitor of DNA base excision repair. Nucleic Acids Res. 33:4711–4724. 2005. View Article : Google Scholar : PubMed/NCBI

26 

Song MQ, Zhu JS, Chen JL, Wang L, Da W, Zhu L and Zhang WP: Synergistic effect of oxymatrine and angiogenesis inhibitor NM-3 on modulating apoptosis in human gastric cancer cells. World J Gastroenterol. 13:1788–1793. 2007. View Article : Google Scholar : PubMed/NCBI

27 

Zhang Y, Piao B, Zhang Y, Hua B, Hou W, Xu W, Qi X, Zhu X, Pei Y and Lin H: Oxymatrine diminishes the side population and inhibits the expression of β-catenin in MCF-7 breast cancer cells. Med Oncol. 28(Suppl 1): S99–S107. 2011. View Article : Google Scholar

28 

Fishel ML and Kelley MR: The DNA base excision repair protein Ape1/Ref-1 as a therapeutic and chemopreventive target. Mol Aspects Med. 28:375–395. 2007. View Article : Google Scholar : PubMed/NCBI

29 

Li Z, Qing Y, Guan W, Li M, Peng Y, Zhang S, Xiong Y and Wang D: Predictive value of APE1, BRCA1, ERCC1 and TUBB3 expression in patients with advanced non-small cell lung cancer (NSCLC) receiving first-line platinum-paclitaxel chemotherapy. Cancer Chemother Pharmacol. 74:777–786. 2014. View Article : Google Scholar : PubMed/NCBI

30 

Izumi T, Hazra TK, Boldogh I, Tomkinson AE, Park MS, Ikeda S and Mitra S: Requirement for human AP endonuclease 1 for repair of 3′-blocking damage at DNA single-strand breaks induced by reactive oxygen species. Carcinogenesis. 21:1329–1334. 2000. View Article : Google Scholar : PubMed/NCBI

31 

Silber JR, Bobola MS, Blank A, Schoeler KD, Haroldson PD, Huynh MB and Kolstoe DD: The apurinic/apyrimidinic endonuclease activity of Ape1/Ref-1 contributes to human glioma cell resistance to alkylating agents and is elevated by oxidative stress. Clin Cancer Res. 8:3008–3018. 2002.PubMed/NCBI

32 

Kunkel TA: The high cost of living. In: American Association for Cancer Research Special Conference: Endogenous sources of mutations; Fort Myers, Florida, USA. 11–15 November 1998; Trends Genet. 15. pp. 93–94. 1999

33 

Loeb LA and Preston BD: Mutagenesis by apurinic/apyrimidinic sites. Annu Rev Genet. 20:201–230. 1986. View Article : Google Scholar : PubMed/NCBI

34 

Bjelland S, Anensen H, Knaevelsrud I and Seeberg E: Cellular effects of 5-formyluracil in DNA. Mutat Res. 486:147–154. 2001. View Article : Google Scholar : PubMed/NCBI

35 

Georgakilas AG, O’Neill P and Stewart RD: Induction and repair of clustered DNA lesions: What do we know so far? Radiat Res. 180:100–109. 2013. View Article : Google Scholar : PubMed/NCBI

36 

Prabhulkar S and Li CZ: Assessment of oxidative DNA damage and repair at single cellular level via real-time monitoring of 8-OHdG biomarker. Biosens Bioelectron. 26:1743–1749. 2010. View Article : Google Scholar : PubMed/NCBI

37 

Kim J, Cha YN and Surh YJ: A protective role of nuclear factor-erythroid 2-related factor-2 (Nrf2) in inflammatory disorders. Mutat Res. 690:12–23. 2010. View Article : Google Scholar

38 

Bapat A, Fishel ML and Kelley MR: Going ape as an approach to cancer therapeutics. Antioxid Redox Signal. 11:651–668. 2009. View Article : Google Scholar :

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Copy and paste a formatted citation
Spandidos Publications style
Wang Z, Xu W, Lin Z, Li C, Wang Y, Yang L and Liu G: Reduced apurinic/apyrimidinic endonuclease activity enhances the antitumor activity of oxymatrine in lung cancer cells. Int J Oncol 49: 2331-2340, 2016.
APA
Wang, Z., Xu, W., Lin, Z., Li, C., Wang, Y., Yang, L., & Liu, G. (2016). Reduced apurinic/apyrimidinic endonuclease activity enhances the antitumor activity of oxymatrine in lung cancer cells. International Journal of Oncology, 49, 2331-2340. https://doi.org/10.3892/ijo.2016.3734
MLA
Wang, Z., Xu, W., Lin, Z., Li, C., Wang, Y., Yang, L., Liu, G."Reduced apurinic/apyrimidinic endonuclease activity enhances the antitumor activity of oxymatrine in lung cancer cells". International Journal of Oncology 49.6 (2016): 2331-2340.
Chicago
Wang, Z., Xu, W., Lin, Z., Li, C., Wang, Y., Yang, L., Liu, G."Reduced apurinic/apyrimidinic endonuclease activity enhances the antitumor activity of oxymatrine in lung cancer cells". International Journal of Oncology 49, no. 6 (2016): 2331-2340. https://doi.org/10.3892/ijo.2016.3734
Copy and paste a formatted citation
x
Spandidos Publications style
Wang Z, Xu W, Lin Z, Li C, Wang Y, Yang L and Liu G: Reduced apurinic/apyrimidinic endonuclease activity enhances the antitumor activity of oxymatrine in lung cancer cells. Int J Oncol 49: 2331-2340, 2016.
APA
Wang, Z., Xu, W., Lin, Z., Li, C., Wang, Y., Yang, L., & Liu, G. (2016). Reduced apurinic/apyrimidinic endonuclease activity enhances the antitumor activity of oxymatrine in lung cancer cells. International Journal of Oncology, 49, 2331-2340. https://doi.org/10.3892/ijo.2016.3734
MLA
Wang, Z., Xu, W., Lin, Z., Li, C., Wang, Y., Yang, L., Liu, G."Reduced apurinic/apyrimidinic endonuclease activity enhances the antitumor activity of oxymatrine in lung cancer cells". International Journal of Oncology 49.6 (2016): 2331-2340.
Chicago
Wang, Z., Xu, W., Lin, Z., Li, C., Wang, Y., Yang, L., Liu, G."Reduced apurinic/apyrimidinic endonuclease activity enhances the antitumor activity of oxymatrine in lung cancer cells". International Journal of Oncology 49, no. 6 (2016): 2331-2340. https://doi.org/10.3892/ijo.2016.3734
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