双氢青蒿素的抗肿瘤作用及机制

贾立峰; 李晓明

doi:10.13201/j.issn.1001-1781.2013.18.021

双氢青蒿素的抗肿瘤作用及机制

贾立峰,
李晓明^,

- 白求恩国际和平医院耳鼻咽喉-头颈外科全军耳鼻咽喉病诊疗中心(石家庄, 050082)

详细信息

通讯作者: 李晓明,E-mail:xml_968@sohu.com

中图分类号: R73

收稿日期: 2012-12-23

The role and mechanism of anticancer of dihydroartemisinin

JIA Lifeng,
LI Xiaoming^,

More Information

Corresponding author: LI Xiaoming, E-mail: xml_968@sohu.com

Received Date: 23 December 2012

摘要

- 双氢青蒿素 /
- 抗肿瘤 /
- 作用 /
- 机制
Abstract: Dihydroartemisinin (DHA) , a semi-synthetic derivative of artemisinin, has recently shown antitumor activity in various cancer cells including cancers of cervix, pancreas, prostate, liver and neuroblastoma.Numerous studies in vivo and in vitro indicate that DHA possesses unique antitumor features and appears to be a promising chemotherapeutic agents.Here we systematically review the advances in research of anticancer of dihydroartemisinin, as well as summarize the mechanisms of its inducing apoptosis, delay cell-cycle, inhibitory cell proliferation and downregulate angiopoiesis.
- dihydroartemisinin /
- anticancer /
- effects /
- mechanism

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参考文献(38)

[1]	LI W D,DONG Y J,TU Y Y,et al.Dihydroarteannuin ameliorates lupus symptom of BXSB mice by inhibiting production of TNF-alpha and blocking the signaling pathway NF-kappa B translocation[J]. Int Immunopharmacol, 2006,6:1243-1250.
[2]	DUTHALER U,HUWYLER J,RINALDI L,et al.Evaluation of the pharmacokinetic profile of artesunate, artemether and their metabolites in sheep naturally infected with Fasciola hepatica[J]. Vet Parasitol, 2011,186:270-280.
[3]	TAWFIK A F, BISHOP S J, AYALP A,et al.Effects of artemisinin,dihydroartemisinin and arteether on immune responses of normal mice[J].Int J Immunopharmacol,1990,12:385-389.
[4]	JIAO Y, GE C M, MENG Q H,et al.Dihydroartemisinin is an inhibitor of ovarian cancer cell growth[J]. Acta Pharmacol Sin, 2007,28:1045-1056.
[5]	GAO N,BUDHRAJA A,CHENG S,et al.Interruption of the MEK/ERK signaling cascade promotes dihydroartemisinin-induced apoptosis in vitro and in vivo[J].Apoptosis,2011,15:511-523.
[6]	LU Y Y,CHEN T S,QU J L,et al.Dihydroartemisinin (DHA) induces caspase-3-dependent apoptosis in human lung adenocarcinoma ASTC-a-1 cells[J]. J Biomed Sci,2009,16:16-16.
[7]	CHAIJAROENKUL W,VIYANANT V,MAHAVORASIRIKUL W,et al.Cytotoxic activity of artemisinin derivatives against cholangiocarcinoma(CL-6) and hepatocarcinoma(Hep-G2) cell lines[J]. Asian Pac J Cancer Prev,2011,12:55-59.
[8]	CABELLO C M,LAMORE S D,BAIR W B,et al.The redox antimalarial dihydroartemisinin targets human metastatic melanoma cells but not primary melanocytes with induction of NOXA-dependent apoptosis[J]. Invest New Drugs,2012,30:1289-1301.
[9]	JI Y,ZHANG Y C,PEI L B,et al.Anti-tumor effects of dihydroartemisinin on human osteosarcoma[J].Mol Cell Biochem,2011,351:99-108.
[10]	ZHANG S,CHEN H,GERHARD G S.Heme synthesis increases artemisinin-induced radical formation and cytotoxicity that can be suppressed by superoxide scavengers[J]. Chem Biol Interact,2010,186:30-35.
[11]	HUANG X J,LI C T,ZHANG W P,et al.Dihydroartemisinin potentiates the cytotoxic effect of temozolomide in rat C6 glioma cells[J].Pharmacology,2008,82:1-9.
[12]	CHEN T,LI M,ZHANG R,et al.Dihydroartemisinin induces apoptosis and sensitizes human ovarian cancer cells to carboplatin therapy[J]. J Cell Mol Med, 2009,13:1358-1370.
[13]	ZHOU H J,ZHANG J L,LI A,et al.Dihydroartemisinin improves the efficiency of chemotherapeutics in lung carcinomas in vivo and inhibits murine Lewis lung carcinoma cell line growth in vitro[J].Cancer Chemother Pharmacol,2010,66:21-29.
[14]	SINGH N P,LAI H.Selective toxicity of dihydroartemisinin and holotransferrin toward human breast cancer cells[J]. Life Sci,2001,70:49-56.
[15]	RAGHAVAMENON A C,MUYIWA A F,DAVIS L K,et al.Dihydroartemisinin induces caspase-8-dependent apoptosis in murine GT1-7 hypothalamic neurons[J].Toxicol Mech Methods,2011,21:367-373.
[16]	LU J J,CHEN S M,ZHANG X W,et al.The anti-cancer activity of dihydroartemisinin is associated with induction of iron-dependent endoplasmic reticulum stress in colorectal carcinoma HCT116 cells[J].Invest New Drugs,2011,29:1276-1283.
[17]	HANDRICK R,ONTIKATZE T,BAUER K D,et al.Dihydroartemisinin induces apoptosis by a Bak-dependent intrinsic pathway[J].Mol Cancer Ther, 2010,9:2497-2510.
[18]	GAO X,LUO Z,XIANG T,et al.Dihydroartemisinin induces endoplasmic reticulum stress-mediated apoptosis in HepG2 human hepatoma cells[J].Tumori,2011,97:771-780.
[19]	WANG S J,SUN B,CHENG Z X,et al.Dihydroartemisinin inhibits angiogenesis in pancreatic cancer by targeting the NF-kappa B pathway[J]. Cancer Chemother Pharmacol, 2011,68:1421-1430.
[20]	LEE J,ZHOU H J,WU X H.Dihydroartemisinin downregulates vascular endothelial growth factor expression and induces apoptosis in chronic myeloid leukemia K562 cells[J].Cancer Chemother Pharmacol,2006,57:213-220.
[21]	WU X H,ZHOU H J,LEE J.Dihydroartemisinin inhibits angiogenesis induced by multiple myeloma RPMI8226 cells under hypoxic conditions via downregulation of vascular endothelial growth factor expression and suppression of vascular endothelial growth factor secretion[J].Anticancer Drugs,2006,17:839-848.
[22]	LU J J, MENG L H, CAI Y J,et al.Dihydroartemisinin induces apoptosis in HL-60 leukemia cells dependent of iron and p38 mitogen-activated protein kinase activation but independent of reactive oxygen species[J].Cancer Biol Ther,2008,7:1017-1023.
[23]	MERCER A E,MAGGS J L,SUN X M, et al.Evidence for the involvement of carbon-centered radicals in the induction of apoptotic cell death by artemisinin compounds[J].J Biol Chem, 2007,282:9372-9382.
[24]	FERREIRA J F,LUTHRIA D L,SASAKI T,et al.Flavonoids from Artemisia annua L. as antioxidants and their potential synergism with artemisinin against malaria and cancer[J].Molecules,2010,15:3135-3170.
[25]	ZHANG C Z,ZHANG H,YUN J,et al.Dihydroartemisinin exhibits antitumor activity toward hepatocellular carcinoma in vitro and in vivo[J].Biochem Pharmacol,2012,83:1278-1289.
[26]	MU D,ZHANG W,CHU D,et al.The role of calcium,P38MAPK in dihydroartemisinin-induced apoptosis of lung cancer PC-14 cells[J].Cancer Chemother Pharmacol,2008,61:639-645.
[27]	HE Q,SHI J,SHEN X L,et al.Dihydroartemisinin upregulates death receptor 5 expression and cooperates with TRAIL to induce apoptosis in human prostate cancer cells[J]. Cancer Biol Ther, 2010,9:819-824.
[28]	HOSOYA K,MURAHARI S,LAIO A,et al.Biological activity of dihydroartemisinin in canine osteosarcoma cell lines[J].Am J Vet Res, 2008,69:519-526.
[29]	JONES M,MERCER A E,STOCKS P A,et al.Antitumour and antimalarial activity of artemisinin-acridine hybrids[J].Bioorg Med Chem Lett, 2009,19:2033-2037.
[30]	D'ALESSANDRO S,BASILICO N,CORBETT Y,et al.Hypoxia modulates the effect of dihydroartemisinin on endothelial cells[J].Biochem Pharmacol,2011,82:476-484.
[31]	AUNG W,SOGAWA C,FURUKAWA T,et al.Anticancer effect of dihydroartemisinin (DHA) in a pancreatic tumor model evaluated by conventional methods and optical imaging[J]. Anticancer Res, 2011,31:1549-1558.
[32]	WU B,HU K,LI S,et al.Dihydroartiminisin inhibits the growth and metastasis of epithelial ovarian cancer[J].Oncol Rep,2012,27:101-108.
[33]	NOORI S,HASSAN Z M,TAGHIKHANI M,et al.Dihydroartemisinin can inhibit calmodulin, calmodulin-dependent phosphodiesterase activity and stimulate cellular immune responses[J]. Int Immunopharmacol, 2010,10:213-217.
[34]	HWANG Y P,YUN H J,KIM H G,et al.Suppression of PMA-induced tumor cell invasion by dihydroartemisinin via inhibition of PKCalpha/Raf/MAPKs and NF-kappaB/AP-1-dependent mechanisms[J]. Biochem Pharmacol,2010,79:1714-1726.
[35]	NOORI S,HASSAN Z M.Dihydroartemisinin shift the immune response towards Th1, inhibit the tumor growth in vitro and in vivo[J].Cell Immunol,2011,271:67-72.
[36]	LU J J,MENG L H,SHANKAVARAM U T,et al.Dihydroartemisinin accelerates c-MYC oncoprotein degradation and induces apoptosis in c-MYC-overexpressing tumor cells[J].Biochem Pharmacol,2010,80:22-30.
[37]	JEMAL A,SIEGEL R,WARD E,et al.Cancer statistics,2007[J].CA Cancer J Clin,2007,57:43-66.
[38]	孟宇,李焰,刘斌,等.双氢青蒿素对人喉癌细胞HeP-2生长抑制作用的实验观察[J]. 第四军医大学学报,2004,25(24):2270-2272.