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CLC number: R96

On-line Access: 2011-04-06

Received: 2010-10-26

Revision Accepted: 2011-02-20

Crosschecked: 2011-03-09

Cited: 24

Clicked: 7151

Citations:  Bibtex RefMan EndNote GB/T7714

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Journal of Zhejiang University SCIENCE B 2011 Vol.12 No.4 P.247-255

http://doi.org/10.1631/jzus.B1000373


Artesunate inhibits growth and induces apoptosis in human osteosarcoma HOS cell line in vitro and in vivo


Author(s):  Qiang Xu, Zhao-xu Li, Hui-qin Peng, Zheng-wang Sun, Rui-lin Cheng, Zhao-ming Ye, Wei-xu Li

Affiliation(s):  Department of Orthopaedics, the Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310009, China, Department of Medical Microbiology and Parasitology, School of Medicine, Zhejiang University, Hangzhou 310058, China

Corresponding email(s):   liweixu@163.com

Key Words:  Artesunate, Human osteosarcoma HOS cells, Apoptosis, Cell cycle, Nude mice, Chemotherapy


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Qiang Xu, Zhao-xu Li, Hui-qin Peng, Zheng-wang Sun, Rui-lin Cheng, Zhao-ming Ye, Wei-xu Li. Artesunate inhibits growth and induces apoptosis in human osteosarcoma HOS cell line in vitro and in vivo[J]. Journal of Zhejiang University Science B, 2011, 12(4): 247-255.

@article{title="Artesunate inhibits growth and induces apoptosis in human osteosarcoma HOS cell line in vitro and in vivo",
author="Qiang Xu, Zhao-xu Li, Hui-qin Peng, Zheng-wang Sun, Rui-lin Cheng, Zhao-ming Ye, Wei-xu Li",
journal="Journal of Zhejiang University Science B",
volume="12",
number="4",
pages="247-255",
year="2011",
publisher="Zhejiang University Press & Springer",
doi="10.1631/jzus.B1000373"
}

%0 Journal Article
%T Artesunate inhibits growth and induces apoptosis in human osteosarcoma HOS cell line in vitro and in vivo
%A Qiang Xu
%A Zhao-xu Li
%A Hui-qin Peng
%A Zheng-wang Sun
%A Rui-lin Cheng
%A Zhao-ming Ye
%A Wei-xu Li
%J Journal of Zhejiang University SCIENCE B
%V 12
%N 4
%P 247-255
%@ 1673-1581
%D 2011
%I Zhejiang University Press & Springer
%DOI 10.1631/jzus.B1000373

TY - JOUR
T1 - Artesunate inhibits growth and induces apoptosis in human osteosarcoma HOS cell line in vitro and in vivo
A1 - Qiang Xu
A1 - Zhao-xu Li
A1 - Hui-qin Peng
A1 - Zheng-wang Sun
A1 - Rui-lin Cheng
A1 - Zhao-ming Ye
A1 - Wei-xu Li
J0 - Journal of Zhejiang University Science B
VL - 12
IS - 4
SP - 247
EP - 255
%@ 1673-1581
Y1 - 2011
PB - Zhejiang University Press & Springer
ER -
DOI - 10.1631/jzus.B1000373


Abstract: 
This paper aims to investigate the effects of artesunate (ART) on growth and apoptosis in human osteosarcoma HOS cell line in vitro and in vivo and to explore the possible underlying mechanisms. Cell viability was measured by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. The induction of apoptosis was detected by light and transmission electron microscopy and flow cytometry. Western blot analysis was used to investigate the related mechanisms. nude mice were further employed to investigate the antitumour activity of ART in vivo. MTT assay results demonstrated that ART selectively inhibits the growth of HOS cells in a dose- and time-dependent manner. Based on the findings of light and transmission electron microscopy, Hoechst 33258 staining, and fluorescein isothiocyanate (FITC)-annexin V staining, the cytotoxicity of ART in HOS cells occurs through apoptosis. With ART treatment, cytosolic cytochrome c was increased, Bax expression was gradually upregulated, Bcl-2 expression was downregulated, and caspase-9 and caspase-3 were activated. Thus, the intrinsic apoptotic pathway may be involved in ART-induced apoptosis. cell cycle analysis by flow cytometry indicated that ART may induce cell cycle arrest at G2/M phase. In nude mice bearing HOS xenograft tumours, ART inhibited tumour growth and regulated the expressions of cleaved caspase-3 and survivin, in agreement with in vitro observations. ART has a selective antitumour activity against human osteosarcoma HOS cells, which may be related to its effects on induction of apoptosis via the intrinsic pathway. The results suggest that ART is a promising candidate for the treatment of osteosarcoma.

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Reference

[1]Adjuik, M., Babiker, A., Garner, P., Olliaro, P., Taylor, W., White, N., 2004. Artesunate combinations for treatment of malaria: meta-analysis. Lancet, 363(9402):9-17.

[2]Altieri, D.C., 2003. Survivin, versatile modulation of cell division and apoptosis in cancer. Oncogene, 22(53):8581-8589.

[3]Berger, T.G., Dieckmann, D., Efferth, T., Schultz, E.S., Funk, J.O., Baur, A., Schuler, G., 2005. Artesunate in the treatment of metastatic uveal melanoma—first experiences. Oncol Reports, 14(6):1599-1603.

[4]Bossy-Wetzel, E., Green, D.R., 1999. Caspases induce cytochrome c release from mitochondria by activating cytosolic factors. J. Biol. Chem., 274(25):17484-17490.

[5]Brama, M., Rhodes, N., Hunt, J., Ricci, A., Teghil, R., Migliaccio, S., Rocca, C.D., Leccisotti, S., Lioi, A., Scandurra, M., et al., 2007. Effect of titanium carbide coating on the osseointegration response in vitro and in vivo. Biomaterials, 28(4):595-608.

[6]Chou, A.J., Gorlick, R., 2006. Chemotherapy resistance in osteosarcoma: current challenges and future directions. Expert Rev. Anticancer Ther., 6(7):1075-1785.

[7]Dell′Eva, R., Pfeffer, U., Vene, R., Anfosso, L., Forlani, A., Albini, A., Efferth, T., 2004. Inhibition of angiogenesis in vivo and growth of Kaposi’s sarcoma xenograft tumors by the anti-malarial artesunate. Biochem. Pharmacol., 68(12):2359-2366.

[8]Doherty, J.F., Sadiq, A.D., Bayo, L., Alloueche, A., Olliaro, P., Milligan, P., von Seidlein, L., Pinder, M., 1999. A randomized safety and tolerability trial of artesunate plus sulfadoxine—pyrimethamine versus sulfadoxine-pyrimethamine alone for the treatment of uncomplicated malaria in Gambian children. Trans. R. Soc. Trop. Med. Hyg., 93(5):543-546.

[9]Du, J.H., Zhang, H.D., Ma, Z.J., Ji, K.M., 2010. Artesunate induces oncosis-like cell death in vitro and has antitumor activity against pancreatic cancer xenografts in vivo. Cancer Chemother. Pharmacol., 65(5):895-902.

[10]Efferth, T., Kaina, B., 2010. Toxicity of the antimalarial artemisinin and its dervatives. Crit. Rev. Toxicol., 40(5):405-421.

[11]Efferth, T., Dunstan, H., Sauerbrey, A., Miyachi, H., Chitambar, C.R., 2001. The anti-malarial artesunate is also active against cancer. Int. J. Oncol., 18(4):767-773.

[12]Efferth, T., Briehl, M.M., Tome, M.E., 2003. Role of antioxidant genes for the activity of artesunate against tumor cells. Int. J. Oncol., 23(4):1231-1235.

[13]Efferth, T., Giaisi, M., Merling, A., Krammer, P.H., Li-Weber, M., 2007. Artesunate induces ROS-mediated apoptosis in doxorubicin-resistant T leukemia cells. PLoS One, 2(8):e693.

[14]Eskes, R., Desagher, S., Antonsson, B., Martinou, J.C., 2000. Bid induces the oligomerization and insertion of Bax into the outer mitochondrial membrane. Mol. Cell Biol., 20(3):929-935.

[15]Fagioli, F., Biasin, E., Mereuta, O.M., Muraro, M., Luksch, R., Ferrari, S., Aglietta, M., Madon, E., 2008. Poor prognosis osteosarcoma: new therapeutic approach. Bone Marrow Transplant., 41(Suppl. 2):S131-S134.

[16]Garcia-Fuster, M.J., Ramos-Miguel, A., Rivero, G., La Harpe, R., Meana, J.J., Garcia-Sevilla, J.A., 2008. Regulation of the extrinsic and intrinsic apoptotic pathways in the prefrontal cortex of short- and long-term human opiate abusers. Neuroscience, 157(1):105-119.

[17]Jaffe, N., 2010. Osteosarcoma: review of the past, impact on the future. The American experience. Cancer Treat. Res., 152(Part 3):239-262.

[18]Li, L.N., Zhang, H.D., Yuan, S.J., Tian, Z.Y., Wang, L., Sun, Z.X., 2007. Artesunate attenuates the growth of human colorectal carcinoma and inhibits hyperactive Wnt/ β-catenin pathway. Int. J. Cancer, 121(6):1360-1365.

[19]Li, P.C., Lam, E., Roos, W.P., Zdzienicka, M.Z., Kaina, B., Efferth, T., 2008. Artesunate derived from traditional Chinese medicine induces DNA damage and repair. Cancer Res., 68(11):4347-4351.

[20]Li, S., Xue, F., Cheng, Z., Yang, X., Wang, S., Geng, F., Pan, L., 2009. Effect of artesunate on inhibiting proliferation and inducing apoptosis of SP2/0 myeloma cells through affecting NFkappaB p65. Int. J. Hematol., 90(4):513-521.

[21]Longhi, A., Porcu, E., Petracchi, S., Versari, M., Conticini, L., Bacci, G., 2000. Reproductive functions in female patients treated with adjuvant and neoadjuvant chemotherapy for localized osteosarcoma of the extremity. Cancer, 89(9):1961-1965.

[22]Mahoney, J.A., Rosen, A., 2005. Apoptosis and autoimmunity. Curr. Opin. Immunol., 17(6):583-588.

[23]Michaelis, M., Kleinschmidt, M.C., Barth, S., Rothweiler, F., Geiler, J., Breitling, R., Mayer, B., Deubzer, H., Witt, O., Kreuter, J., et al., 2010. Anti-cancer effects of artesunate in a panel of chemoresistant neuroblastoma cell lines. Biochem. Pharmacol., 79(2):130-136.

[24]Mirabello, L., Troisi, R.J., Savage, S.A., 2009. Osteosarcoma incidence and survival rates from 1973 to 2004: data from the Surveillance, Epidemiology, and End Results Program. Cancer, 115(7):1531-1543.

[25]Osaka, E., Suzuki, T., Osaka, S., Yoshida, Y., Sugita, H., Asami, S., Tabata, K., Sugitani, M., Nemoto, N., Ryu, J., 2007. Survivin expression levels as independent predictors of survival for osteosarcoma patients. J. Orthop. Res., 25(1):116-121.

[26]Rasheed, S.A., Efferth, T., Asangani, I.A., Allgayer, H., 2010. First evidence that the anti-malarial drug artesunate inhibits invasion and in vivo metastasis in lung cancer by targeting essential extracellular proteases. Int. J. Cancer, 127(6):1475-1485.

[27]Schwartz, C.L., Gorlick, R., Teot, L., Krailo, M., Chen, Z., Goorin, A., Grier, H.E., Bernstein, M.L., Meyers, P., 2007. Multiple drug resistance in osteogenic sarcoma: INT0133 from the Children’s Oncology Group. J. Clin. Oncol., 25(15):2057-2062.

[28]Taylor, W.R., Terlouw, D.J., Olliaro, P.L., White, N.J., Brasseur, P., ter Kuile, F.O., 2006. Use of weight-for-age-data to optimize tablet strength and dosing regimens for a new fixed-dose artesunate-amodiaquine combination for treating falciparum malaria. Bull. World Health Organ., 84(12):956-964.

[29]Uren, A.G., Wong, L., Pakusch, M., Fowler, K.J., Burrows, F.J., Vaux, D.L., Choo, K.H., 2000. Survivin and the inner centromere protein INCENP show similar cell-cycle localization and gene knockout phenotype. Curr. Biol., 10(21):1319-1328.

[30]Walensky, L.D., 2006. BCL-2 in the crosshairs: tipping the balance of life and death. Cell Death Differ., 13(8):1339-1350.

[31]Weerasinghe, K.L., Galappaththy, G., Fernando, W.P., Wickremasinghe, D.R., Faizal, H.M., Wickremasinghe, A.R., 2002. A safety and efficacy trial of artesunate, sulphadoxine-pyrimethamine and primaquine in P. falciparum malaria. Ceylon Med. J., 47(3):83-85.

[32]Yang, J., Liu, X., Bhalla, K., Kim, C.N., Ibrado, A.M., Cai, J., Peng, T.I., Jones, D.P., Wang, X., 1997. Prevention of apoptosis by Bcl-2: release of cytochrome c from mitochondria blocked. Science, 275(5303):1129-1132.

[33]Zhou, H.J., Wang, W.Q., Wu, G.D., Lee, J., Li, A., 2007. Artesunate inhibits angiogenesis and downregulates vascular endothelial growth factor expression in chronic myeloid leukemia K562 cells. Vascul. Pharmacol., 47(2-3):131-138.

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