Tetra-arsenic tetra-sulfide induces cell cycle arrest and apoptosis in retinoic acid-resistant acute promyelocytic leukemia cells

Wang,Yuan; He,Peng‑Cheng; Qi,Jun; Liu,Yan‑Feng; Zhang,Mei

doi:10.3892/br.2015.466

Tetra-arsenic tetra-sulfide induces cell cycle arrest and apoptosis in retinoic acid-resistant acute promyelocytic leukemia cells

Authors:
- Yuan Wang
- Peng‑Cheng He
- Jun Qi
- Yan‑Feng Liu
- Mei Zhang
View Affiliations

Affiliations: Department of Hematology, The First Affiliated Hospital, Xi'an Jiaotong University Medical College, Xi'an, Shaanxi 710061, P.R. China, Institute of Xi'an Blood Bank, Shaanxi Blood Center, Xi'an, Shaanxi 710061, P.R. China
Published online on: May 21, 2015 https://doi.org/10.3892/br.2015.466
Pages: 583-587

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

Previous studies have shown that the therapeutic action of tetra-arsenic tetra-sulfide (As4S4) is effective for acute promyelocytic leukemia. However, the molecular mechanism of the action of As4S4 in retinoic acid-resistant acute promyelocytic leukemia (APL) therapy remains unclear. In the present study, the signaling of the cytotoxic effects induced by As4S4 on retinoic acid‑resistant APL NB4‑R1 cells was investigated. A time‑dependent increase in cell death and DNA cleavage was observed following As4S4 treatment. Changes in B‑cell lymphoma 2 and Bax accompanied by the activation of caspase‑3 and cleavage of poly ADP‑ribose polymerase were observed as actions of As4S4. As4S4 induced an accumulation of NB4‑R1 cells in the S and G2/M phases, as detected by flow cytometry. Therefore, the present results suggest that As4S4‑mediated apoptosis in NB4-R1 cells involves a mitochondria-dependent pathway.

View Figures

View References

1	De Braekeleer E, Douet-Guilbert N and De Braekeleer M: RARA fusion genes in acute promyelocytic leukemia: A review. Expert Rev Hematol. 7:347–357. 2014. View Article : Google Scholar : PubMed/NCBI
2	Lo-Coco F, Avvisati G, Vignetti M, Thiede C, Orlando SM, Iacobelli S, Ferrara F, Fazi P, Cicconi L, Di Bona E, et al: Gruppo Italiano Malattie Ematologiche dell'Adulto; German-Austrian Acute Myeloid Leukemia Study Group; Study Alliance Leukemia: Retinoic acid and arsenic trioxide for acute promyelocytic leukemia. N Engl J Med. 369:111–121. 2013. View Article : Google Scholar : PubMed/NCBI
3	Fenaux P, Chevret S, Guerci A, Fegueux N, Dombret H, Thomas X, Sanz M, Link H, Maloisel F, Gardin C, et al: Long-term follow-up confirms the benefit of all-trans retinoic acid in acute promyelocytic leukemia. European APL group. Leukemia. 14:1371–1377. 2000. View Article : Google Scholar : PubMed/NCBI
4	Westervelt P, Brown RA, Adkins DR, Khoury H, Curtin P, Hurd D, Luger SM, Ma MK, Ley TJ and DiPersio JF: Sudden death among patients with acute promyelocytic leukemia treated with arsenic trioxide. Blood. 98:266–271. 2001. View Article : Google Scholar : PubMed/NCBI
5	Lu DP, Qiu JY, Jiang B, Wang Q, Liu KY, Liu YR and Chen SS: Tetra-arsenic tetra-sulfide for the treatment of acute promyelocytic leukemia: A pilot report. Blood. 99:3136–3143. 2002. View Article : Google Scholar : PubMed/NCBI
6	Zhu HH, Wu DP, Jin J, Li JY, Ma J, Wang JX, Jiang H, Chen SJ and Huang XJ: Oral tetra-arsenic tetra-sulfide formula versus intravenous arsenic trioxide as first-line treatment of acute promyelocytic leukemia: A multicenter randomized controlled trial. J Clin Oncol. 31:4215–4221. 2013. View Article : Google Scholar : PubMed/NCBI
7	Qi J, Zhang M, He P, et al: Establishment of two-dimensional electrophoresis proteomic profiles of retinoid acid resistant human acute promyelocytic leukemia NB4-R1 cells with apoptosis induced by realgar. Chin J Integr Med. 31:391–396. 2011.
8	Wang XB, Gao HY, Hou BL, Huang J, Xi RG and Wu LJ: Nanoparticle realgar powders induce apoptosis in U937 cells through caspase MAPK and mitochondrial pathways. Arch Pharm Res. 30:653–658. 2007. View Article : Google Scholar : PubMed/NCBI
9	Tse WP, Cheng CH, Che CT, Zhao M, Fan RQ and Lin ZX: Realgar-mediated growth inhibition on HaCaT human keratinocytes is associated with induction of apoptosis. Int J Mol Med. 24:189–196. 2009.PubMed/NCBI
10	Rong Y and Distelhorst CW: Bcl-2 protein family members: Versatile regulators of calcium signaling in cell survival and apoptosis. Annu Rev Physiol. 70:73–91. 2008. View Article : Google Scholar : PubMed/NCBI
11	Brajusković G, Orolicki SV, Cerović S, Usaj SK, Marjanović S and Romac S: Bcl-2 and Bax protein interaction in B-lymphocytes of peripheral blood in patients with chronic lymphocytic leukemia. Vojnosanit Pregl. 62:357–363. 2005.(In Serbian). View Article : Google Scholar : PubMed/NCBI
12	Martinou JC and Youle RJ: Mitochondria in apoptosis: Bcl-2 family members and mitochondrial dynamics. Dev Cell. 21:92–101. 2011. View Article : Google Scholar : PubMed/NCBI
13	Sikdar S, Mukherjee A, Ghosh S and Khuda-Bukhsh AR: Condurango glycoside-rich components stimulate DNA damage-induced cell cycle arrest and ROS-mediated caspase-3 dependent apoptosis through inhibition of cell-proliferation in lung cancer, in vitro and in vivo. Environ Toxicol Pharmacol. 37:300–314. 2014. View Article : Google Scholar : PubMed/NCBI
14	Tong X, Han X, Yu B, Yu M, Jiang G, Ji J and Dong S: Role of gap junction intercellular communication in testicular leydig cell apoptosis induced by oxaliplatin via the mitochondrial pathway. Oncol Rep. 33:207–214. 2015.PubMed/NCBI
15	Bayascas JR, Yuste VJ, Solé C, Sánchez-López I, Segura MF, Perera R and Comella JX: Characterization of splice variants of human caspase-activated DNase with CIDE-N structure and function. FEBS Lett. 566:234–240. 2004. View Article : Google Scholar : PubMed/NCBI
16	Boulares AH, Zoltoski AJ, Contreras FJ, Yakovlev AG, Yoshihara K and Smulson ME: Regulation of DNAS1L3 endonuclease activity by poly(ADP-ribosyl)ation during etoposide-induced apoptosis. Role of poly(ADP-ribose) polymerase-1 cleavage in endonuclease activation. J Biol Chem. 277:372–378. 2002. View Article : Google Scholar : PubMed/NCBI
17	Chen WX, Zhang F, Yang HC, et al: The effect of realgar on apoptosis of transplanted ovarian SKOV3 carcinoma cells in nude mice. Tumor. 27:787–790. 2007.
18	Chen SY, Liu SX and Li XM: The dual effects of realgar on acute promyelocytic leukemia cell: Inducing apoptosis and promoting differentiation. J Xi'an Jiaotong Univ. 23:401–404. 2002.