Dihydroartemisinin-induced apoptosis in human acute monocytic leukemia cells

Cao,Jia‑Tian; Mo,Hui‑Min; Wang,Yue; Zhao,Kai; Zhang,Tian‑Tian; Wang,Chang‑Qian; Xu,Kai‑Lin; Han,Zhi‑Hua

doi:10.3892/ol.2017.7644

Dihydroartemisinin-induced apoptosis in human acute monocytic leukemia cells

Authors:
- Jia‑Tian Cao
- Hui‑Min Mo
- Yue Wang
- Kai Zhao
- Tian‑Tian Zhang
- Chang‑Qian Wang
- Kai‑Lin Xu
- Zhi‑Hua Han
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Affiliations: Department of Cardiology, The Ninth People's Hospital, Shanghai Jiaotong University Medical School, Shanghai 200011, P.R. China, Institute of Hematology, Xuzhou Medical University, Xuzhou, Jiangsu 221002, P.R. China
Published online on: December 19, 2017 https://doi.org/10.3892/ol.2017.7644
Pages: 3178-3184

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Abstract

Dihydroartemisinin (DHA) is a derivative of artemisinin. The present study aimed to investigate whether DHA induces apoptosis in the THP‑1 human acute monocytic leukemia cell line (AMoL), and to identify the relative molecular mechanisms. The results of the present study demonstrated that the viability of THP‑1 cells were inhibited by DHA in a dose‑ and time‑dependent manner, which was accompanied by morphological characteristics associated with apoptosis. After 24 h of 200 µM DHA treatment, the proportion of apoptotic cells was significantly increased compared with the untreated controls (P<0.01). In addition, DHA downregulated the levels of B‑cell lymphoma (Bcl)‑2, protein kinase B (Akt)1, Akt2 and Akt3 gene expression, and increased the expression of the Bcl‑2‑associated X protein apoptosis regulator. The protein expression of phospho‑Akt and phospho‑extracellular signal‑regulated kinase (ERK) was also decreased, and the protein expression level of cleaved caspase‑3 was increased following treatment with DHA. Therefore, DHA may induce apoptosis in the AMoL THP‑1 cell line via currently unknown underlying molecular mechanisms, including the downregulation of ERK and Akt, and the activation of caspase-3.

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1	Ommen HB: Monitoring minimal residual disease in acute myeloid leukaemia: A review of the current evolving strategies. Ther Adv Hematol. 7:3–16. 2016. View Article : Google Scholar : PubMed/NCBI
2	Peng H, Wang H, Xue P, Hou Y, Dong J, Zhou T, Qu W, Peng S, Li J, Carmichael PL, et al: Suppression of NRF2-ARE activity sensitizes chemotherapeutic agent-induced cytotoxicity in human acute monocytic leukemia cells. Toxicol Appl Pharmacol. 292:1–7. 2016. View Article : Google Scholar : PubMed/NCBI
3	Guo Y, Shan Q, Gong Y, Lin J, Shi F, Shi R and Yang X: Curcumin induces apoptosis via simultaneously targeting AKT/mTOR and RAF/MEK/ERK survival signaling pathways in human leukemia THP-1 cells. Pharmazie. 69:229–233. 2014.PubMed/NCBI
4	Ozpolat B, Akar U, Steiner M, Zorrilla-Calancha I, Tirado-Gomez M, Colburn N, Danilenko M, Kornblau S and Berestein GL: Programmed cell death-4 tumor suppressor protein contributes to retinoic acid-induced terminal granulocytic differentiation of human myeloid leukemia cells. Mol Cancer Res. 5:95–108. 2007. View Article : Google Scholar : PubMed/NCBI
5	Murashige N, Tabanda R and Zalusky R: Occurrence of acute monocytic leukemia in a case of untreated Waldenstrom's macroglobulinemia. Am J Hematol. 71:94–97. 2002. View Article : Google Scholar : PubMed/NCBI
6	Cline MJ: Histiocytes and histiocytosis. Blood. 84:2840–2853. 1994.PubMed/NCBI
7	Kumar RK, Basu S, Lemke HD, Jankowski J, Kratz K, Lendlein A and Tetali SD: Effect of extracts of poly(ether imide) microparticles on cytotoxicity, ROS generation and proinflammatory effects on human monocytic (THP-1) cells. Clin Hemorheol Microcirc. 61:667–680. 2016. View Article : Google Scholar : PubMed/NCBI
8	Li Y: Qinghaosu (artemisinin): Chemistry and pharmacology. Acta Pharmacol Sin. 33:1141–1146. 2012. View Article : Google Scholar : PubMed/NCBI
9	Lin AJ, Klayman DL and Milhous WK: Antimalarial activity of new water-soluble dihydroartemisinin derivatives. J Med Chem. 30:2147–2150. 1987. View Article : Google Scholar : PubMed/NCBI
10	Ashley EA, McGready R, Hutagalung R, Phaiphun L, Slight T, Proux S, Thwai KL, Barends M, Looareesuwan S, White NJ and Nosten F: A randomized, controlled study of a simple, once-daily regimen of dihydroartemisinin-piperaquine for the treatment of uncomplicated, multidrug-resistant falciparum malaria. Clin Infect Dis. 41:425–432. 2005. View Article : Google Scholar : PubMed/NCBI
11	Gordi T and Lepist EI: Artemisinin derivatives: Toxic for laboratory animals, safe for humans? Toxicol Lett. 147:99–107. 2004. View Article : Google Scholar : PubMed/NCBI
12	Mi YJ, Geng GJ, Zou ZZ, Gao J, Luo XY, Liu Y, Li N, Li CL, Chen YQ, Yu XY and Jiang J: Dihydroartemisinin inhibits glucose uptake and cooperates with glycolysis inhibitor to induce apoptosis in non-small cell lung carcinoma cells. PLoS One. 10:e01204262015. View Article : Google Scholar : PubMed/NCBI
13	Liu W, Wang DW, Yu SY, Cao Y, Yang L, E XQ, Yao GJ and Bi ZG: The effect of dihydroartemisinin on the proliferation, metastasis and apoptosis of human osteosarcoma cells and its mechanism. J Biol Regul Homeost Agents. 29:335–342. 2015.PubMed/NCBI
14	Feng X, Li L, Jiang H, Jiang K, Jin Y and Zheng J: Dihydroartemisinin potentiates the anticancer effect of cisplatin via mTOR inhibition in cisplatin-resistant ovarian cancer cells: Involvement of apoptosis and autophagy. Biochem Biophys Res Commun. 444:376–381. 2014. View Article : Google Scholar : PubMed/NCBI
15	Park J, Lai HC, Singh M, Sasaki T and Singh NP: Development of a dihydroartemisinin-resistant Molt-4 leukemia cell line. Anticancer Res. 34:2807–2810. 2014.PubMed/NCBI
16	Chan HW, Singh NP and Lai HC: Cytotoxicity of dihydroartemisinin toward Molt-4 cells attenuated by N-tert-butyl-alpha-phenylnitrone and deferoxamine. Anticancer Res. 33:4389–4393. 2013.PubMed/NCBI
17	Schmittgen TD and Livak KJ: Analyzing real-time PCR data by the comparative C(T) method. Nat Protoc. 3:1101–1108. 2008. View Article : Google Scholar : PubMed/NCBI
18	Zhang D, Wang Q, Zhu T, Cao J, Zhang X, Wang J, Wang X, Li Y, Shen B and Zhang J: RACK1 promotes the proliferation of THP1 acute myeloid leukemia cells. Mol Cell Biochem. 384:197–202. 2013. View Article : Google Scholar : PubMed/NCBI
19	Zeng C, Wang W, Yu X, Yang L, Chen S and Li Y: Pathways related to PMA-differentiated THP1 human monocytic leukemia cells revealed by RNA-Seq. Sci China Life Sci. 58:1282–1287. 2015. View Article : Google Scholar : PubMed/NCBI
20	Evans FJ and Hilton JH: Polymyositis associated with acute Nonocytic leukemia: Case report and review of the literature. Can Med Assoc J. 91:1272–1275. 1964.PubMed/NCBI
21	Wang Y, Ma L, Wang C, Sheng G, Feng L and Yin C: Autocrine motility factor receptor promotes the proliferation of human acute monocytic leukemia THP-1 cells. Int J Mol Med. 36:627–632. 2015. View Article : Google Scholar : PubMed/NCBI
22	Jain SK, Sahu R, Walker LA and Tekwani BL: A parasite rescue and transformation assay for antileishmanial screening against intracellular Leishmania donovani amastigotes in THP1 human acute monocytic leukemia cell line. Journal of visualized experiments. 70:e40542012.
23	Tu YY: TU You-you won Lasker Debakey clinical medical research award-for her outstanding achievements in studies on artemisinin. Zhongguo Zhong Xi Yi Jie He Za Zhi. 31:13012011.(In Chinese). PubMed/NCBI
24	Dong YJ, Li WD and Tu YY: Effect of dihydro-qinghaosu on auto-antibody production, TNF alpha secretion and pathologic change of lupus nephritis in BXSB mice. Zhongguo Zhong Xi Yi Jie He Za Zhi. 23:676–679. 2003.(In Chinese). PubMed/NCBI
25	Zhang CZ, Zhang H, Yun J, Chen GG and Lai PB: Dihydroartemisinin exhibits antitumor activity toward hepatocellular carcinoma in vitro and in vivo. Biochem Pharmacol. 83:1278–1289. 2012. View Article : Google Scholar : PubMed/NCBI
26	Feng MX, Hong JX, Wang Q, Fan YY, Yuan CT, Lei XH, Zhu M, Qin A, Chen HX and Hong D: Dihydroartemisinin prevents breast cancer-induced osteolysis via inhibiting both breast cancer cells and osteoclasts. Sci Rep. 6:190742016. View Article : Google Scholar : PubMed/NCBI
27	Wang Z, Hu W, Zhang JL, Wu XH and Zhou HJ: Dihydroartemisinin induces autophagy and inhibits the growth of iron-loaded human myeloid leukemia K562 cells via ROS toxicity. FEBS Open Bio. 2:103–112. 2012. View Article : Google Scholar : PubMed/NCBI
28	Zhao X, Zhong H, Wang R, Liu D, Waxman S, Zhao L and Jing Y: Dihydroartemisinin and its derivative induce apoptosis in acute myeloid leukemia through Noxa-mediated pathway requiring iron and endoperoxide moiety. Oncotarget. 6:5582–5596. 2015.PubMed/NCBI
29	Lim SG, Suk K and Lee WH: Reverse signaling from LIGHT promotes pro-inflammatory responses in the human monocytic leukemia cell line, THP-1. Cell Immunol. 285:10–17. 2013. View Article : Google Scholar : PubMed/NCBI
30	Teng CL, Han SM, Wu WC, Hsueh CM, Tsai JR, Hwang WL and Hsu SL: Mechanistic aspects of lauryl gallate-induced differentiation and apoptosis in human acute myeloid leukemia cells. Food Chem Toxicol. 71:197–206. 2014. View Article : Google Scholar : PubMed/NCBI
31	Shi D, Xu Y, Du X, Chen X, Zhang X, Lou J, Li M and Zhuo J: Co-treatment of THP-1 cells with naringenin and curcumin induces cell cycle arrest and apoptosis via numerous pathways. Mol Med Rep. 12:8223–8228. 2015. View Article : Google Scholar : PubMed/NCBI
32	Olesen LH, Aggerholm A, Andersen BL, Nyvold CG, Guldberg P, Nørgaard JM and Hokland P: Molecular typing of adult acute myeloid leukaemia: Significance of translocations, tandem duplications, methylation, and selective gene expression profiling. Br J Haematol. 131:457–467. 2005. View Article : Google Scholar : PubMed/NCBI
33	Ruvolo PP, Qiu Y, Coombes KR, Zhang N, Neeley ES, Ruvolo VR, Hail N Jr, Borthakur G, Konopleva M, Andreeff M and Kornblau SM: Phosphorylation of GSK3α/β correlates with activation of AKT and is prognostic for poor overall survival in acute myeloid leukemia patients. BBA Clin. 4:59–68. 2015. View Article : Google Scholar : PubMed/NCBI