JS-K promotes apoptosis by inducing ROS production in human prostate cancer cells

Qiu,Mingning; Chen,Lieqian; Tan,Guobin; Ke,Longzhi; Zhang,Sai; Chen,Hege; Liu,Jianjun

doi:10.3892/ol.2016.5535

March-2017 Volume 13 Issue 3

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March-2017 Volume 13 Issue 3

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JS-K promotes apoptosis by inducing ROS production in human prostate cancer cells

Authors:
- Mingning Qiu
- Lieqian Chen
- Guobin Tan
- Longzhi Ke
- Sai Zhang
- Hege Chen
- Jianjun Liu
View Affiliations / Copyright

Affiliations: Laboratory of Urology, Guangdong Medical University, Zhanjiang, Guangdong 524001, P.R. China

Copyright: © Qiu et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
Pages: 1137-1142
|
Published online on: December 27, 2016

https://doi.org/10.3892/ol.2016.5535
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Abstract

Reactive oxygen species (ROS) are chemical species that alter redox status, and are responsible for inducing carcinogenesis. The purpose of the present study was to assess the effects of the glutathione S transferase-activated nitric oxide donor prodrug, JS‑K, on ROS accumulation and on proliferation and apoptosis in human prostate cancer cells. Cell proliferation and apoptosis, ROS accumulation and the activation of the mitochondrial signaling pathway were measured. The results demonstrated that JS‑K may inhibit prostate cancer cell growth in a dose‑ and time‑dependent manner, and induce ROS accumulation and apoptosis in a dose‑dependent manner. With increasing concentrations of JS‑K, expression of pro‑apoptotic proteins increased, but Bcl‑2 expression decreased. Additionally, the antioxidant N‑acetylcysteine reversed JS‑K‑induced cell apoptosis; conversely, the pro‑oxidant glutathione disulfide exacerbated JS‑K‑induced apoptosis. In conclusion, the data suggest that JS-K induces prostate cancer cell apoptosis by increasing ROS levels.

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1	Shami PJ, Saavedra JE, Wang LY, Bonifant CL, Diwan BA, Singh SV, Gu Y, Fox SD, Buzard GS, Citro ML, et al: JS-K, a glutathione/glutathione S-transferase-activated nitric oxide donor of the diazeniumdiolate class with potent antineoplastic activity. Mol Cancer Ther. 2:409–417. 2003.PubMed/NCBI
2	Kiziltepe T, Hideshima T, Ishitsuka K, Ocio EM, Raje N, Catley L, Li CQ, Trudel LJ, Yasui H, Vallet S, et al: JS-K, a GST-activated nitric oxide generator, induces DNA double-strand breaks, activates DNA damage response pathways, and induces apoptosis in vitro and in vivo in human multiple myeloma cells. Blood. 110:709–718. 2007. View Article : Google Scholar : PubMed/NCBI
3	Hsieh HJ, Liu CA, Huang B, Tseng AH and Wang DL: Shear-induced endothelial mechanotransduction: The interplay between reactive oxygen species (ROS) and nitric oxide (NO) and the pathophysiological implications. J Biomed Sci. 21:32014. View Article : Google Scholar : PubMed/NCBI
4	Maciag AE, Chakrapani H, Saavedra JE, Morris NL, Holland RJ, Kosak KM, Shami PJ, Anderson LM and Keefer LK: The nitric oxide prodrug JS-K is effective against non-small-cell lung cancer cells in vitro and in vivo: Involvement of reactive oxygen species. J Pharmacol Exp Ther. 336:313–320. 2011. View Article : Google Scholar : PubMed/NCBI
5	Laschak M, Spindler KD, Schrader AJ, Hessenauer A, Streicher W, Schrader M and Cronauer MV: JS-K, a glutathione/glutathione S-transferase-activated nitric oxide releasing prodrug inhibits androgen receptor and WNT-signaling in prostate cancer cells. BMC Cancer. 12:1302012. View Article : Google Scholar : PubMed/NCBI
6	Ray PD, Huang BW and Tsuji Y: Reactive oxygen species (ROS) homeostasis and redox regulation in cellular signaling. Cell Signal. 24:981–990. 2012. View Article : Google Scholar : PubMed/NCBI
7	Wu WS: The signaling mechanism of ROS in tumor progression. Cancer Metastasis Rev. 25:695–705. 2006. View Article : Google Scholar : PubMed/NCBI
8	Das TP, Suman S and Damodaran C: Induction of reactive oxygen species generation inhibits epithelial-mesenchymal transition and promotes growth arrest in prostate cancer cells. Mol Carcinog. 53:537–547. 2014. View Article : Google Scholar : PubMed/NCBI
9	Nie F, Zhang X, Qi Q, Yang L, Yang Y, Liu W, Lu N, Wu Z, You Q and Guo Q: Reactive oxygen species accumulation contributes to gambogic acid-induced apoptosis in human hepatoma SMMC-7721 cells. Toxicology. 260:60–67. 2009. View Article : Google Scholar : PubMed/NCBI
10	Allan LA and Clarke PR: Apoptosis and autophagy: Regulation of caspase-9 by phosphorylation. FEBS J. 276:6063–6073. 2009. View Article : Google Scholar : PubMed/NCBI
11	Nicholson DW and Thornberry NA: Caspases: Killer proteases. Trends Biochem Sci. 22:299–306. 1997. View Article : Google Scholar : PubMed/NCBI
12	Satoh MS and Lindahl T: Role of poly (ADP-ribose) formation in DNA repair. Nature. 356:356–358. 1992. View Article : Google Scholar : PubMed/NCBI
13	Oliver FJ, Menissier-de Murcia J and de Murcia G: Poly(ADP-ribose) polymerase in the cellular response to DNA damage, apoptosis, and disease. Am J Hum Genet. 64:1282–1288. 1999. View Article : Google Scholar : PubMed/NCBI
14	Pöhland T, Wagner S, MahyarRoemer M and Roemer K: Bax and Bak are the critical complementary effectors of colorectal cancer cell apoptosis by chemopreventive resveratrol. Anticancer Drugs. 17:471–478. 2006. View Article : Google Scholar : PubMed/NCBI
15	Tasyriq M, Najmuldeen IA, In LL, Mohamad K, Awang K and Hasima N: 7α-Hydroxy-β-Sitosterol from chisocheton tomentosus induces apoptosis via dysregulation of cellular Bax/Bcl-2 ratio and cell cycle arrest by downregulating ERK1/2 activation. Evid Based Complement Alternat Med. 2012:7653162012. View Article : Google Scholar : PubMed/NCBI

Journals

International Journal of Molecular Medicine

International Journal of Oncology

Molecular Medicine Reports

Oncology Reports

Experimental and Therapeutic Medicine

Oncology Letters

Biomedical Reports

Molecular and Clinical Oncology

World Academy of Sciences Journal

International Journal of Functional Nutrition

International Journal of Epigenetics

Medicine International

JS-K promotes apoptosis by inducing ROS production in human prostate cancer cells

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