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Article Open Access

Dual effects of arsenic trioxide on tumor cells and the potential underlying mechanisms

  • Authors:
    • Xiao Zhang
    • Dahai Yu
    • Huaize Geng
    • Fengmei Li
    • Lin Lv
    • Lei Zhao
    • Caichuan Yan
    • Baoxin Li
  • View Affiliations / Copyright

    Affiliations: Department of Pharmacology, College of Pharmacy, Harbin Medical University, Harbin, Heilongjiang 150086, P.R. China
    Copyright: © Zhang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Pages: 3812-3820
    |
    Published online on: July 5, 2018
       https://doi.org/10.3892/ol.2018.9086
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Abstract

The human ether‑a‑go‑go related gene (hERG) encodes the rapid delayed rectifier K+ channel. hERG not only serves an important role in heart muscle and cardiomyocyte excitability by regulating action potential repolarization, but also represents a selective advantage for cancer cell proliferation. Arsenic trioxide is a traditional Chinese medicine, which has been previously identified as an efficient tumor suppressor, particularly in the treatment of acute pro‑myelocytic leukemia. However, studies have also reported that long‑term exposure to arsenicals may lead to the formation of malignant tumors. In the present study, the effect of low‑dose arsenic trioxide on the proliferation and apoptosis of tumor cells was investigated, as were the potential underlying mechanisms of this effect. The data demonstrated that low‑dose arsenic trioxide (0.1 µM) enhanced the viability and apoptosis of tumor cells expressing hERG channels following long‑term incubation. However, in tumor cells lacking hERG channels, low‑dose arsenic trioxide had no effect. Therefore, we hypothesized that this hormesis effect of low‑dose arsenic trioxide on tumor cells may be associated with the hERG channel. Furthermore, low dose arsenic trioxide promoted the hERG‑channel current by changing the kinetics of channel gating and prolonging the open‑channel stage. Simultaneously, high‑dose As2O3 (1 or 10 µM) significantly reduced the expression of hERG in tumor cells compared with the control group, which resulted in reduced proliferation rate and promotion of apoptotic rate. The results of the present study demonstrate that the dual effects of arsenic trioxide on hERG channels vary according to concentration, resulting in the dual effects on tumor cells. This provides a theoretical basis for the potential clinical application of arsenic trioxide, suggesting that hERG channels are an important target in preventing and treating tumorigenesis during arsenicosis.
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1 

Curran ME, Splawski I, Timothy KW, Vincent GM, Green ED and Keating MT: A molecular basis for cardiac arrhythmia: HERG mutations cause long QT syndrome. Cell. 80:795–803. 1995. View Article : Google Scholar : PubMed/NCBI

2 

Haverkamp W, Breithardt G, Camm AJ, Janse MJ, Rosen MR, Antzelevitch C, Escande D, Franz M, Malik M, Moss A and Shah R: The potential for QT prolongation and proarrhythmia by non-antiarrhythmic drugs: Clinical and regulatory implications. Report on a policy conference of the European Society of Cardiology. Eur Heart J. 21:1216–1231. 2000. View Article : Google Scholar : PubMed/NCBI

3 

Farkas AS and Nattel S: Minimizing repolarization-related proarrhythmic risk in drug development and clinical practice. Drugs. 70:573–603. 2010. View Article : Google Scholar : PubMed/NCBI

4 

Kannankeril P, Roden DM and Darbar D: Drug-induced long QT syndrome. Pharmacol Rev. 62:760–781. 2010. View Article : Google Scholar : PubMed/NCBI

5 

Bi LL, Ma Q and Wang SQ: Treatment of 32 cases with recurring acute promyelocytic leukemia with tablets of composite natural indigo. Zhonghua Er Ke Za Zhi. 43:702–703. 2005.(In Chinese). PubMed/NCBI

6 

Chen GQ, Shi XG, Tang W, Xiong SM, Zhu J, Cai X, Han ZG, Ni JH, Shi GY, Jia PM, et al: Use of arsenic trioxide (As2O3) in the treatment of acute promyelocytic leukemia (APL): I. As2O3 exerts dose-dependent dual effects on APL cells. Blood. 89:3345–3353. 1997.PubMed/NCBI

7 

Zhang TC, Cao EH, Li JF, Ma W and Qin JF: Induction of apoptosis and inhibition of human gastric cancer MGC-803 cell growth by arsenic trioxide. Eur J Cancer. 35:1258–1263. 1999. View Article : Google Scholar : PubMed/NCBI

8 

Ye J, Li A, Liu Q, Wang X and Zhou J: Inhibition of mitogen-activated protein kinase kinase enhances apoptosis induced by arsenic trioxide in human breast cancer MCF-7 cells. Clin Exp Pharmacol Physiol. 32:1042–1048. 2005. View Article : Google Scholar : PubMed/NCBI

9 

Wang C, Chen X, Wu J, Liu H, Ji Z, Shi H, Gao C, Han D, Wang L, Liu Y, et al: Low-dose arsenic trioxide enhances 5-aminolevulinic acid-induced PpIX accumulation and efficacy of photodynamic therapy in human glioma. J Photochem Photobiol B. 127:61–67. 2013. View Article : Google Scholar : PubMed/NCBI

10 

Raja WK, Satti J, Liu G and Castracane J: Dose response of MTLn3 cells to serial dilutions of arsenic trioxide and ionizing radiation. Dose Response. 11:29–40. 2013. View Article : Google Scholar : PubMed/NCBI

11 

Ganapathy S, Li P, Fagman J, Yu T, Lafontant J, Zhang G and Chen C: Low doses of arsenic, via perturbing p53, promotes tumorigenesis. Toxicol Appl Pharmacol. 306:98–104. 2016. View Article : Google Scholar : PubMed/NCBI

12 

Becchetti A, Crescioli S, Zanieri F, Petroni G, Mercatelli R, Coppola S, Gasparoli L, D'Amico M, Pillozzi S, Crociani O, et al: The conformational state of hERG1 channels determines integrin association, downstream signaling, and cancer progression. Sci Signal. 10:pii: eaaf3236. 2017. View Article : Google Scholar : PubMed/NCBI

13 

Crociani O, Lastraioli E, Boni L, Pillozzi S, Romoli MR, D'Amico M, Stefanini M, Crescioli S, Masi A, Taddei A, et al: hERG1 channels regulate VEGF-A secretion in human gastric cancer: Clinicopathological correlations and therapeutical implications. Clin Cancer Res. 20:1502–1512. 2014. View Article : Google Scholar : PubMed/NCBI

14 

Fortunato A: The role of hERG1 ion channels in epithelial-mesenchymal transition and the capacity of riluzole to reduce cisplatin resistance in colorectal cancer cells. Cell Oncol (Dordr). 40:367–378. 2017. View Article : Google Scholar : PubMed/NCBI

15 

Ficker E, Kuryshev YA, Dennis AT, Obejero-Paz C, Wang L, Hawryluk P, Wible BA and Brown AM: Mechanisms of arsenic-induced prolongation of cardiac repolarization. Mol Pharmacol. 66:33–44. 2004. View Article : Google Scholar : PubMed/NCBI

16 

Wan X, Dennis AT, Obejero-Paz C, Overholt JL, Heredia-Moya J, Kirk KL and Ficker E: Oxidative inactivation of the lipid phosphatase phosphatase and tensin homolog on chromosome ten (PTEN) as a novel mechanism of acquired long QT syndrome. J Biol Chem. 286:2843–2852. 2011. View Article : Google Scholar : PubMed/NCBI

17 

Chen SZ, Jiang M and Zhen YS: Correlation of HERG K+ channel protein expression to chemosensitivity of tumor cells to doxorubicin and its modulation by erythromycin. Ai Zheng. 24:924–929. 2005.(In Chinese). PubMed/NCBI

18 

Zhang Y, Dong Z, Jin L, Zhang K, Zhao X, Fu J, Gong Y, Sun M, Yang B and Li B: Arsenic trioxide-induced hERG K(+) channel deficiency can be rescued by matrine and oxymatrine through up-regulating transcription factor Sp1 expression. Biochem Pharmacol. 85:59–68. 2013. View Article : Google Scholar : PubMed/NCBI

19 

Nicholson GM, Blanche T, Mansfield K and Tran Y: Differential blockade of neuronal voltage-gated Na(+) and K(+) channels by antidepressant drugs. Eur J Pharmacol. 452:35–48. 2002. View Article : Google Scholar : PubMed/NCBI

20 

Pace C, Dagda R and Angermann J: Antioxidants protect against arsenic induced mitochondrial Cardio-toxicity. Toxics. 5:pii: E38. 2017. View Article : Google Scholar : PubMed/NCBI

21 

Sarkar A and Paul B: The global menace of arsenic and its conventional remediation-A critical review. Chemosphere. 158:37–49. 2016. View Article : Google Scholar : PubMed/NCBI

22 

Oremland RS and Stolz JF: Arsenic, microbes and contaminated aquifers. Trends Microbiol. 13:45–49. 2005. View Article : Google Scholar : PubMed/NCBI

23 

Orloff K, Mistry K and Metcalf S: Biomonitoring for environmental exposures to arsenic. J Toxicol Environ Health B Crit Rev. 12:509–524. 2009. View Article : Google Scholar : PubMed/NCBI

24 

Reeve BB, Burke LB, Chiang YP, Clauser SB, Colpe LJ, Elias JW, Fleishman J, Hohmann AA, Johnson-Taylor WL, Lawrence W, et al: Enhancing measurement in health outcomes research supported by Agencies within the US Department of Health and Human Services. Qual Life Res. 16 Suppl 1:S175–S186. 2007. View Article : Google Scholar

25 

Xu WX, Liu Y, Liu SZ, Zhang Y, Qiao GF and Yan J: Arsenic trioxide exerts a double effect on osteoblast growth in vitro. Environ Toxicol Pharmacol. 38:412–419. 2014. View Article : Google Scholar : PubMed/NCBI

26 

Lin X, Chen Q, Huang C and Xu X: CYLD promotes TNF-α-induced cell necrosis mediated by RIP-1 in human lung cancer cells. Mediators Inflamm. 2016:15427862016. View Article : Google Scholar : PubMed/NCBI

27 

Wang H, Zhang Y, Cao L, Han H, Wang J, Yang B, Nattel S and Wang Z: HERG K+ channel, a regulator of tumor cell apoptosis and proliferation. Cancer Res. 62:4843–4848. 2002.PubMed/NCBI

28 

Li P, Ninomiya H, Kurata Y, Kato M, Miake J, Yamamoto Y, Igawa O, Nakai A, Higaki K, Toyoda F, et al: Reciprocal control of hERG stability by Hsp70 and Hsc70 with implication for restoration of LQT2 mutant stability. Circ Res. 108:458–468. 2011. View Article : Google Scholar : PubMed/NCBI

29 

Dong ZX, Zhao X, Gu DF, Shi YQ, Zhang J, Hu XX, Hu MQ, Yang BF and Li BX: Comparative effects of liensinine and neferine on the human ether-a-go-go-related gene potassium channel and pharmacological activity analysis. Cell Physiol Biochem. 29:431–442. 2012. View Article : Google Scholar : PubMed/NCBI

30 

Yang Z, Prinsen JK, Bersell KR, Shen W, Yermalitskaya L, Sidorova T, Luis PB, Hall L, Zhang W, Du L, et al: Azithromycin causes a novel proarrhythmic syndrome. Circ Arrhythm Electrophysiol. 10:pii: e003560. 2017. View Article : Google Scholar

31 

Staudacher I, Jehle J, Staudacher K, Pledl HW, Lemke D, Schweizer PA, Becker R, Katus HA and Thomas D: HERG K+ channel-dependent apoptosis and cell cycle arrest in human glioblastoma cells. PLoS One. 9:e881642014. View Article : Google Scholar : PubMed/NCBI

32 

Shi YQ, Yan M, Liu LR, Zhang X, Wang X, Geng HZ, Zhao X and Li BX: High glucose represses hERG K+ channel expression through trafficking inhibition. Cell Physiol Biochem. 37:284–296. 2015. View Article : Google Scholar : PubMed/NCBI

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Copy and paste a formatted citation
Spandidos Publications style
Zhang X, Yu D, Geng H, Li F, Lv L, Zhao L, Yan C and Li B: Dual effects of arsenic trioxide on tumor cells and the potential underlying mechanisms. Oncol Lett 16: 3812-3820, 2018.
APA
Zhang, X., Yu, D., Geng, H., Li, F., Lv, L., Zhao, L. ... Li, B. (2018). Dual effects of arsenic trioxide on tumor cells and the potential underlying mechanisms. Oncology Letters, 16, 3812-3820. https://doi.org/10.3892/ol.2018.9086
MLA
Zhang, X., Yu, D., Geng, H., Li, F., Lv, L., Zhao, L., Yan, C., Li, B."Dual effects of arsenic trioxide on tumor cells and the potential underlying mechanisms". Oncology Letters 16.3 (2018): 3812-3820.
Chicago
Zhang, X., Yu, D., Geng, H., Li, F., Lv, L., Zhao, L., Yan, C., Li, B."Dual effects of arsenic trioxide on tumor cells and the potential underlying mechanisms". Oncology Letters 16, no. 3 (2018): 3812-3820. https://doi.org/10.3892/ol.2018.9086
Copy and paste a formatted citation
x
Spandidos Publications style
Zhang X, Yu D, Geng H, Li F, Lv L, Zhao L, Yan C and Li B: Dual effects of arsenic trioxide on tumor cells and the potential underlying mechanisms. Oncol Lett 16: 3812-3820, 2018.
APA
Zhang, X., Yu, D., Geng, H., Li, F., Lv, L., Zhao, L. ... Li, B. (2018). Dual effects of arsenic trioxide on tumor cells and the potential underlying mechanisms. Oncology Letters, 16, 3812-3820. https://doi.org/10.3892/ol.2018.9086
MLA
Zhang, X., Yu, D., Geng, H., Li, F., Lv, L., Zhao, L., Yan, C., Li, B."Dual effects of arsenic trioxide on tumor cells and the potential underlying mechanisms". Oncology Letters 16.3 (2018): 3812-3820.
Chicago
Zhang, X., Yu, D., Geng, H., Li, F., Lv, L., Zhao, L., Yan, C., Li, B."Dual effects of arsenic trioxide on tumor cells and the potential underlying mechanisms". Oncology Letters 16, no. 3 (2018): 3812-3820. https://doi.org/10.3892/ol.2018.9086
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