Skip to main content
SpringerLink
Log in

Activity of Artemisinin-Type Compounds Against Cancer Cells

  • Chapter
  • First Online:
Book cover Evidence and Rational Based Research on Chinese Drugs

Abstract

Clinical Oncology strives for complete remission of patients with cancer, but still crusades against multidrug resistance of various cancers. Scientists and clinicians have been challenged to identify new potent anticancer compounds with new targeting strategies. Traditional Chinese Medicine (TCM) provides a large spectrum of medicinal plants containing many biocompounds that possess anticancer activities. These represent a source of molecules that may have antiproliferative effects on a variety of cancers.

Our interest on natural products from TCM was raised in the 1990s by sesquiterpene lactones of the artemisinin type from Artemisia annua L., which exert antimalarial and profound anticancer activity.

Besides novel preclinical developments, we review and discuss the benefit of adjuvant therapies with artemisinin in combination with known chemotherapeutics. Moreover, we depict new biotechnological production methods for meeting the worldwide increasing demand of artemisinin since the WHO officially recommends it for the treatment of malaria.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 219.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 279.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 279.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  • Abdin MZ, Israr M, Rehman RU, Jain SK (2003) Artemisinin, a novel antimalarial drug: biochemical and molecular approaches for enhanced production. Planta Med 69:289–299

    Article  PubMed  CAS  Google Scholar 

  • Achen MG, Jeltsch M, Kukk E, Makinen T, Vitali A, Wilks AF, Alitalo K, Stacker SA (1998) Vascular endothelial growth factor D (VEGF-D) is a ligand for the tyrosine kinases VEGF receptor 2 (Flk1) and VEGF receptor 3 (Flt4). Proc Natl Acad Sci USA 95:548–553

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  • Anfosso L, Efferth T, Albini A, Pfeffer U (2006) Microarray expression profiles of angiogenesis-related genes predict tumor cell response to artemisinins. Pharmacogenomics J 6:269–278

    PubMed  CAS  Google Scholar 

  • Asimus S, Elsherbiny D, Hai TN, Jansson B, Huong NV, Petzold MG, Simonsson US, Ashton M (2007) Artemisinin antimalarials moderately affect cytochrome P450 enzyme activity in healthy subjects. Fundam Clin Pharmacol 21:307–316

    Article  PubMed  CAS  Google Scholar 

  • Asimus S, Hai TN, Van Huong N, Ashton M (2008) Artemisinin and CYP2A6 activity in healthy subjects. Eur J Clin Pharmacol 64:283–292

    Article  PubMed  CAS  Google Scholar 

  • Bapiro TE, Andersson TB, Otter C, Hasler JA, Masimirembwa CM (2002) Cytochrome P450 1A1/2 induction by antiparasitic drugs: dose-dependent increase in ethoxyresorufin O-deethylase activity and mRNA caused by quinine, primaquine and albendazole in HepG2 cells. Eur J Clin Pharmacol 58:537–542

    Article  PubMed  CAS  Google Scholar 

  • Bapiro TE, Sayi J, Hasler JA, Jande M, Rimoy G, Masselle A, Masimirembwa CM (2005) Artemisinin and thiabendazole are potent inhibitors of cytochrome P450 1A2 (CYP1A2) activity in humans. Eur J Clin Pharmacol 61:755–761

    Article  PubMed  CAS  Google Scholar 

  • Berger TG, Dieckmann D, Efferth T, Schultz ES, Funk JO, Baur A, Schuler G (2005) Artesunate in the treatment of metastatic uveal melanoma–first experiences. Oncol Rep 14:1599–1603

    PubMed  CAS  Google Scholar 

  • Bertea CM, Freije JR, van der Woude H, Verstappen FW, Perk L, Marquez V, De Kraker JW, Posthumus MA, Jansen BJ, de Groot A, Franssen MC, Bouwmeester HJ (2005) Identification of intermediates and enzymes involved in the early steps of artemisinin biosynthesis in Artemisia annua. Planta Med 71:40–47

    Article  PubMed  CAS  Google Scholar 

  • Brewer TG, Peggins JO, Grate SJ, Petras JM, Levine BS, Weina PJ, Swearengen J, Heiffer MH, Schuster BG (1994a) Neurotoxicity in animals due to arteether and artemether. Trans R Soc Trop Med Hyg 88(Suppl 1):S33–S36

    Article  PubMed  Google Scholar 

  • Brewer TG, Grate SJ, Peggins JO, Weina PJ, Petras JM, Levine BS, Heiffer MH, Schuster BG (1994b) Fatal neurotoxicity of arteether and artemether. Am J Trop Med Hyg 51:251–259

    PubMed  CAS  Google Scholar 

  • Broxterman HJ, Lankelma J, Hoekman K (2003) Resistance to cytotoxic and anti-angiogenic anticancer agents: similarities and differences. Drug Resist Updat 6:111–127

    Article  PubMed  CAS  Google Scholar 

  • Burk O, Arnold KA, Nussler AK, Schaeffeler E, Efimova E, Avery BA, Avery MA, Fromm MF, Eichelbaum M (2005) Antimalarial artemisinin drugs induce cytochrome P450 and MDR1 expression by activation of xenosensors pregnane X receptor and constitutive androstane receptor. Mol Pharmacol 67:1954–1965

    Article  PubMed  CAS  Google Scholar 

  • Cabello CM, Lamore SD, Bair WB 3rd, Qiao S, Azimian S, Lesson JL, Wondrak GT (2012) The redox antimalarial dihydroartemisinin targets human metastatic melanoma cells but not primary melanocytes with induction of NOXA-dependent apoptosis. Invest New Drugs 30(4):1289–1301

    Article  PubMed  CAS  Google Scholar 

  • Carrara VI, Phyo AP, Nwee P, Soe M, Htoo H, Arunkamomkiri J, Singhasivanon P, Nosten F (2008) Auditory assessment of patients with acute uncomplicated plasmodium falciparum malaria treated with three-day mefloquine-artesunate on the north-western border of Thailand. Malar J 7:233

    Article  PubMed  Google Scholar 

  • Chen HH, Zhou HJ, Fang X (2003) Inhibition of human cancer cell line growth and human umbilical vein endothelial cell angiogenesis by artemisinin derivatives in vitro. Pharmacol Res 48:231–236

    Article  PubMed  CAS  Google Scholar 

  • Chen HH, Zhou HJ, Wang WQ, Wu GD (2004a) Antimalarial dihydroartemisinin also inhibits angiogenesis. Cancer Chemother Pharmacol 53:423–432

    Article  PubMed  CAS  Google Scholar 

  • Chen HH, Zhou HJ, Wu GD, Lou XE (2004b) Inhibitory effects of artesunate on angiogenesis and on expressions of vascular endothelial growth factor and VEGF receptor KDR/flk-1. Pharmacology 71:1–9

    Article  PubMed  CAS  Google Scholar 

  • Chen T, Li M, Zhang R, Wang H (2008) Dihydroartemisinin induces apoptosis and sensitizes human ovarian cancer cells to carboplatin therapy. J Cell Mol Med 13(7):1358–1370

    Article  PubMed  CAS  Google Scholar 

  • Chen H, Sun B, Pan S, Jiang H, Sun X (2009) Dihydroartemisinin inhibits growth of pancreatic cancer cells in vitro and in vivo. Anticancer Drugs 20:131–140

    Article  PubMed  CAS  Google Scholar 

  • Curry EA 3rd, Murry DJ, Yoder C, Fife K, Armstrong V, Nakshatri H, O’Connell M, Sweeney CJ (2004) Phase I dose escalation trial of feverfew with standardized doses of parthenolide in patients with cancer. Invest New Drugs 22:299–305

    Article  PubMed  CAS  Google Scholar 

  • D’Alessandro S, Gelati M, Basilico N, Parati EA, Haynes RK, Taramelli D (2007) Differential effects on angiogenesis of two antimalarial compounds, dihydroartemisinin and artemisone: implications for embryotoxicity. Toxicology 241:66–74

    Article  PubMed  CAS  Google Scholar 

  • Davis TM, Karunajeewa HA, Ilett KF (2005) Artemisinin-based combination therapies for uncomplicated malaria. Med J Aust 182:181–185

    PubMed  Google Scholar 

  • De Jesus-Gonzalez L, Weathers PJ (2003) Tetraploid Artemisia annua hairy roots produce more artemisinin than diploids. Plant Cell Rep 21:809–813

    PubMed  Google Scholar 

  • De Kraker JW (2003) Hydroxylation of sesquiterpenes by enzymes from chicory (Cichorium intybus L.) roots. Tetrahedron 59:409–418

    Article  Google Scholar 

  • Delabays N, Simonnet X, Gaudin M (2001) The genetics of artemisinin content in Artemisia annua L. and the breeding of high yielding cultivars. Curr Med Chem 8:1795–1801

    Article  PubMed  CAS  Google Scholar 

  • 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 68:2359–2366

    Article  PubMed  CAS  Google Scholar 

  • Disbrow GL, Baege AC, Kierpiec KA, Yuan H, Centeno JA, Thibodeaux CA, Hartmann D, Schlegel R (2005) Dihydroartemisinin is cytotoxic to papillomavirus-expressing epithelial cells in vitro and in vivo. Cancer Res 65:10854–10861

    Article  PubMed  CAS  Google Scholar 

  • Dondorp A, Nosten F, Stepniewska K, Day N, White N (2005) Artesunate versus quinine for treatment of severe falciparum malaria: a randomised trial. Lancet 366:717–725

    Article  PubMed  CAS  Google Scholar 

  • Efferth T (2005) Mechanistic perspectives for 1,2,4-trioxanes in anti-cancer therapy. Drug Resist Updat 8:85–97

    Article  PubMed  CAS  Google Scholar 

  • Efferth T (2006) Molecular pharmacology and pharmacogenomics of artemisinin and its derivatives in cancer cells. Curr Drug Targets 7:407–421

    Article  PubMed  CAS  Google Scholar 

  • Efferth T (2007) Willmar Schwabe Award 2006: antiplasmodial and antitumor activity of artemisinin–from bench to bedside. Planta Med 73:299–309

    Article  PubMed  CAS  Google Scholar 

  • Efferth T, Grassmann R (2000) Impact of viral oncogenesis on responses to anti-cancer drugs and irradiation. Crit Rev Oncog 11:165–187

    PubMed  CAS  Google Scholar 

  • Efferth T, Kaina B (2010) Toxicity of the antimalarial artemisinin and its derivatives. Crit Rev Toxicol 40:405–421

    Article  PubMed  CAS  Google Scholar 

  • Efferth T, Oesch F (2004) Oxidative stress response of tumor cells: microarray-based comparison between artemisinins and anthracyclines. Biochem Pharmacol 68:3–10

    Article  PubMed  CAS  Google Scholar 

  • Efferth T, Volm M (1993) Reversal of doxorubicin-resistance in sarcoma 180 tumor cells by inhibition of different resistance mechanisms. Cancer Lett 70:197–202

    Article  PubMed  CAS  Google Scholar 

  • Efferth T, Volm M (2005a) Pharmacogenetics for individualized cancer chemotherapy. Pharmacol Ther 107:155–176

    Article  PubMed  CAS  Google Scholar 

  • Efferth T, Volm M (2005b) Glutathione-related enzymes contribute to resistance of tumor cells and low toxicity in normal organs to artesunate. In Vivo 19:225–232

    PubMed  CAS  Google Scholar 

  • Efferth T, Mattern J, Volm M (1992) Immunohistochemical detection of P glycoprotein, glutathione S transferase and DNA topoisomerase II in human tumors. Oncology 49:368–375

    Article  PubMed  CAS  Google Scholar 

  • Efferth T, Rucker G, Falkenberg M, Manns D, Olbrich A, Fabry U, Osieka R (1996) Detection of apoptosis in KG-1a leukemic cells treated with investigational drugs. Arzneimittelforschung 46:196–200

    PubMed  CAS  Google Scholar 

  • Efferth T, Fabry U, Osieka R (1997) Apoptosis and resistance to daunorubicin in human leukemic cells. Leukemia 11:1180–1186

    Article  PubMed  CAS  Google Scholar 

  • Efferth T, Dunstan H, Sauerbrey A, Miyachi H, Chitambar CR (2001) The anti-malarial artesunate is also active against cancer. Int J Oncol 18:767–773

    PubMed  CAS  Google Scholar 

  • Efferth T, Fabry U, Osieka R (2002a) Interleukin-6 affects melphalan-induced DNA damage and repair in human multiple myeloma cells. Anticancer Res 22:231–234

    PubMed  CAS  Google Scholar 

  • Efferth T, Olbrich A, Bauer R (2002b) mRNA expression profiles for the response of human tumor cell lines to the antimalarial drugs artesunate, arteether, and artemether. Biochem Pharmacol 64:617–623

    Article  PubMed  CAS  Google Scholar 

  • Efferth T, Davey M, Olbrich A, Rucker G, Gebhart E, Davey R (2002c) Activity of drugs from traditional Chinese medicine toward sensitive and MDR1- or MRP1-overexpressing multidrug-resistant human CCRF-CEM leukemia cells. Blood Cells Mol Dis 28:160–168

    Article  PubMed  Google Scholar 

  • Efferth T, Sauerbrey A, Olbrich A, Gebhart E, Rauch P, Weber HO, Hengstler JG, Halatsch ME, Volm M, Tew KD, Ross DD, Funk JO (2003a) Molecular modes of action of artesunate in tumor cell lines. Mol Pharmacol 64:382–394

    Article  PubMed  CAS  Google Scholar 

  • Efferth T, Briehl MM, Tome ME (2003b) Role of antioxidant genes for the activity of artesunate against tumor cells. Int J Oncol 23:1231–1235

    PubMed  CAS  Google Scholar 

  • Efferth T, Benakis A, Romero MR, Tomicic M, Rauh R, Steinbach D, Hafer R, Stamminger T, Oesch F, Kaina B, Marschall M (2004a) Enhancement of cytotoxicity of artemisinins toward cancer cells by ferrous iron. Free Radic Biol Med 37:998–1009

    Article  PubMed  CAS  Google Scholar 

  • Efferth T, Ramirez T, Gebhart E, Halatsch ME (2004b) Combination treatment of glioblastoma multiforme cell lines with the anti-malarial artesunate and the epidermal growth factor receptor tyrosine kinase inhibitor OSI-774. Biochem Pharmacol 67:1689–1700

    Article  PubMed  CAS  Google Scholar 

  • Efferth T, Giaisi M, Merling A, Krammer PH, Li-Weber M (2007) Artesunate induces ROS-mediated apoptosis in doxorubicin-resistant T leukemia cells. PLoS One 2:e693

    Article  PubMed  CAS  Google Scholar 

  • Efferth T, Romero MR, Wolf DG, Stamminger T, Marin JJ, Marschall M (2008) The antiviral activities of artemisinin and artesunate. Clin Infect Dis 47:804–811

    Article  PubMed  CAS  Google Scholar 

  • Elmarakby SA, El-Feraly FS, Elsohly HN, Croom EM, Hufford CD (1987) Microbial transformation studies on arteannuin B. J Nat Prod 50:903–909

    Article  PubMed  CAS  Google Scholar 

  • Elsherbiny DA, Asimus SA, Karlsson MO, Ashton M, Simonsson US (2008) A model based assessment of the CYP2B6 and CYP2C19 inductive properties by artemisinin antimalarials: implications for combination regimens. J Pharmacokinet Pharmacodyn 35:203–217

    Article  PubMed  CAS  Google Scholar 

  • Folkman J (1992) The role of angiogenesis in tumor growth. Semin Cancer Biol 3:65–71

    PubMed  CAS  Google Scholar 

  • Fujita T, Felix K, Pinkaew D, Hutadilok-Towatana N, Liu Z, Fujise K (2008) Human fortilin is a molecular target of dihydroartemisinin. FEBS Lett 582:1055–1060

    Article  PubMed  CAS  Google Scholar 

  • Gallo MA, Kaufman D (1997) Antagonistic and agonistic effects of tamoxifen: significance in human cancer. Semin Oncol 24:S1-71–S1-80

    Google Scholar 

  • Gao N, Budhraja A, Cheng S, Liu EH, Huang C, Chen J, Yang Z, Chen D, Zhang Z, Shi X (2011) Interruption of the MEK/ERK signaling cascade promotes dihydroartemisinin-induced apoptosis in vitro and in vivo. Apoptosis 16:511–523

    Article  PubMed  CAS  Google Scholar 

  • Genovese RF, Newman DB (2008) Understanding artemisinin-induced brainstem neurotoxicity. Arch Toxicol 82:379–385

    Article  PubMed  CAS  Google Scholar 

  • Genovese RF, Newman DB, Li Q, Peggins JO, Brewer TG (1998a) Dose-dependent brainstem neuropathology following repeated arteether administration in rats. Brain Res Bull 45:199–202

    Article  PubMed  CAS  Google Scholar 

  • Genovese RF, Newman DB, Petras JM, Brewer TG (1998b) Behavioral and neural toxicity of arteether in rats. Pharmacol Biochem Behav 60:449–458

    Article  PubMed  CAS  Google Scholar 

  • Gordi T, Lepist EI (2004) Artemisinin derivatives: toxic for laboratory animals, safe for humans? Toxicol Lett 147:99–107

    Article  PubMed  CAS  Google Scholar 

  • Gordi T, Xie R, Huong NV, Huong DX, Karlsson MO, Ashton M (2005) A semiphysiological pharmacokinetic model for artemisinin in healthy subjects incorporating autoinduction of metabolism and saturable first-pass hepatic extraction. Br J Clin Pharmacol 59:189–198

    Article  PubMed  CAS  Google Scholar 

  • Grant S, Qiao L, Dent P (2002) Roles of ERBB family receptor tyrosine kinases, and downstream signaling pathways, in the control of cell growth and survival. Front Biosci 7:d376–d389

    Article  PubMed  CAS  Google Scholar 

  • Hampton T (2005) Collaboration hopes microbe factories can supply key antimalaria drug. JAMA 293:785–787

    Article  PubMed  CAS  Google Scholar 

  • Handrick R, Ontikatze T, Bauer KD, Freier F, Rübel A, Dürig J, Belka C, Jendrossek V (2010) Dihydroartemisinin induces apoptosis by a Bak-dependent intrinsic pathway. Mol Cancer Ther 9:2497–2510

    Article  PubMed  CAS  Google Scholar 

  • Haynes RK (2001) Artemisinin and derivatives: the future for malaria treatment? Curr Opin Infect Dis 14:719–726

    Article  PubMed  CAS  Google Scholar 

  • He F, Bi HC, Xie ZY, Zuo Z, Li JK, Li X, Zhao LZ, Chen X, Huang M (2007) Rapid determination of six metabolites from multiple cytochrome P450 probe substrates in human liver microsome by liquid chromatography/mass spectrometry: application to high-throughput inhibition screening of terpenoids. Rapid Commun Mass Spectrom 21:635–643

    Article  PubMed  CAS  Google Scholar 

  • He Q, Shi J, Shen XL, An J, Sun H, Wang L, Hu YJ, Sun Q, Fu LC, Sheikh MS, Huang Y (2010) Dihydroartemisinin upregulates death receptor 5 expression and cooperates with TRAIL to induce apoptosis in human prostate cancer cells. Cancer Biol Ther 9:819–824

    Article  PubMed  CAS  Google Scholar 

  • Hofheinz W, Burgin H, Gocke E, Jaquet C, Masciadri R, Schmid G, Stohler H, Urwyler H (1994) Ro 42–1611 (arteflene), a new effective antimalarial: chemical structure and biological activity. Trop Med Parasitol 45:261–265

    PubMed  CAS  Google Scholar 

  • Hou J, Wang D, Zhang R, Wang H (2008) Experimental therapy of hepatoma with artemisinin and its derivatives: in vitro and in vivo activity, chemosensitization, and mechanisms of action. Clin Cancer Res 14:5519–5530

    Article  PubMed  CAS  Google Scholar 

  • Huang XJ, Ma ZQ, Zhang WP, Lu YB, Wei EQ (2007) Dihydroartemisinin exerts cytotoxic effects and inhibits hypoxia inducible factor-1alpha activation in C6 glioma cells. J Pharm Pharmacol 59:849–856

    Article  PubMed  CAS  Google Scholar 

  • Huang XJ, Li CT, Zhang WP, Lu YB, Fang SH, Wei EQ (2008) Dihydroartemisinin potentiates the cytotoxic effect of temozolomide in rat C6 glioma cells. Pharmacology 82:1–9

    Article  PubMed  CAS  Google Scholar 

  • Huan-huan C, Li-Li Y, Shang-Bin L (2004) Artesunate reduces chicken chorioallantoic membrane neovascularisation and exhibits antiangiogenic and apoptotic activity on human microvascular dermal endothelial cell. Cancer Lett 211:163–173

    Article  PubMed  CAS  Google Scholar 

  • Hutagalung R, Htoo H, Nwee P, Arunkamomkiri J, Zwang J, Carrara VI, Ashley E, Singhasivanon P, White NJ, Nosten F (2006) A case–control auditory evaluation of patients treated with artemether-lumefantrine. Am J Trop Med Hyg 74:211–214

    PubMed  CAS  Google Scholar 

  • Hwang YP, Yun HJ, Kim HG, Han EH, Lee GW, Jeong HG (2010) Suppression of PMA-induced tumor cell invasion by dihydroartemisinin via inhibition of PKCalpha/Raf/MAPKs and NF-kappaB/AP-1-dependent mechanisms. Biochem Pharmacol 79:1714–1726

    Article  PubMed  CAS  Google Scholar 

  • Ishikawa TAK (1996) Transport of glutathione S-conjugates from cancer cells: function and structure of GS-X pump. Taylor and Francis, London, pp 199–211

    Google Scholar 

  • Jiao Y, Ge CM, Meng QH, Cao JP, Tong J, Fan SJ (2007) Dihydroartemisinin is an inhibitor of ovarian cancer cell growth. Acta Pharmacol Sin 28:1045–1056

    Article  PubMed  CAS  Google Scholar 

  • Joukov V, Pajusola K, Kaipainen A, Chilov D, Lahtinen I, Kukk E, Saksela O, Kalkkinen N, Alitalo K (1996) A novel vascular endothelial growth factor, VEGF-C, is a ligand for the Flt4 (VEGFR-3) and KDR (VEGFR-2) receptor tyrosine kinases. EMBO J 15:290–298

    PubMed  CAS  Google Scholar 

  • Kamchonwongpaisan S, McKeever P, Hossler P, Ziffer H, Meshnick SR (1997) Artemisinin neurotoxicity: neuropathology in rats and mechanistic studies in vitro. Am J Trop Med Hyg 56:7–12

    PubMed  CAS  Google Scholar 

  • Kelter G, Steinbach D, Konkimalla VB, Tahara T, Taketani S, Fiebig HH, Efferth T (2007) Role of transferrin receptor and the ABC transporters ABCB6 and ABCB7 for resistance and differentiation of tumor cells towards artesunate. PLoS One 2:e798

    Article  PubMed  CAS  Google Scholar 

  • Kerbel R, Folkman J (2002) Clinical translation of angiogenesis inhibitors. Nat Rev Cancer 2:727–739

    Article  PubMed  CAS  Google Scholar 

  • Kim SJ, Kim MS, Lee JW, Lee CH, Yoo H, Shin SH, Park MJ, Lee SH (2006) Dihydroartemisinin enhances radiosensitivity of human glioma cells in vitro. J Cancer Res Clin Oncol 132:129–135

    Article  PubMed  CAS  Google Scholar 

  • Klayman DL (1985) Qinghaosu (artemisinin): an antimalarial drug from China. Science 228:1049–1055

    Article  PubMed  CAS  Google Scholar 

  • Konkimalla VB, Blunder M, Korn B, Soomro SA, Jansen H, Chang W, Posner GH, Bauer R, Efferth T (2008) Effect of artemisinins and other endoperoxides on nitric oxide-related signaling pathway in RAW 264.7 mouse macrophage cells. Nitric Oxide 19:184–191

    Article  PubMed  CAS  Google Scholar 

  • Konkimalla VB, McCubrey JA, Efferth T (2009) The role of downstream signaling pathways of the epidermal growth factor receptor for Artesunate’s activity in cancer cells. Curr Cancer Drug Targets 9:72–80

    Article  PubMed  CAS  Google Scholar 

  • Lai H, Sasaki T, Singh NP (2005) Targeted treatment of cancer with artemisinin and artemisinin-tagged iron-carrying compounds. Expert Opin Ther Targets 9:995–1007

    Article  PubMed  CAS  Google Scholar 

  • Laughlin JC (1994) Agricultural production of artemisinin–a review. Trans R Soc Trop Med Hyg 88(Suppl 1):S21–S22

    Article  PubMed  Google Scholar 

  • Lee J, Zhou HJ, Wu XH (2006) Dihydroartemisinin downregulates vascular endothelial growth factor expression and induces apoptosis in chronic myeloid leukemia K562 cells. Cancer Chemother Pharmacol 57:213–220

    Article  PubMed  CAS  Google Scholar 

  • Lenihan JR, Tsuruta H, Diola D, Renninger NS, Regentin R (2008) Developing an industrial artemisinic acid fermentation process to support the cost-effective production of antimalarial artemisinin-based combination therapies. Biotechnol Prog 24:1026–1032

    Article  PubMed  CAS  Google Scholar 

  • Li Y, Wu YL (1998) How Chinese scientists discovered qinghaosu (artemisinin) and developed its derivatives? what are the future perspectives? Med Trop (Mars) 58:9–12

    CAS  Google Scholar 

  • Li QG, Mog SR, Si YZ, Kyle DE, Gettayacamin M, Milhous WK (2002) Neurotoxicity and efficacy of arteether related to its exposure times and exposure levels in rodents. Am J Trop Med Hyg 66:516–525

    PubMed  CAS  Google Scholar 

  • Li LN, Zhang HD, Yuan SJ, Tian ZY, Wang L, Sun ZX (2007) Artesunate attenuates the growth of human colorectal carcinoma and inhibits hyperactive Wnt/beta-catenin pathway. Int J Cancer 121:1360–1365

    Article  PubMed  CAS  Google Scholar 

  • Li H, van Berlo D, Shi T, Speit G, Knaapen AM, Borm PJ, Albrecht C, Schins RP (2008) Curcumin protects against cytotoxic and inflammatory effects of quartz particles but causes oxidative DNA damage in a rat lung epithelial cell line. Toxicol Appl Pharmacol 227:115–124

    Article  PubMed  CAS  Google Scholar 

  • Lindahl AL, Olsson ME, Mercke P, Tollbom O, Schelin J, Brodelius M, Brodelius PE (2006) Production of the artemisinin precursor amorpha-4,11-diene by engineered Saccharomyces cerevisiae. Biotechnol Lett 28:571–580

    Article  PubMed  CAS  Google Scholar 

  • Liu C, Zhao Y, Wang Y (2006) Artemisinin: current state and perspectives for biotechnological production of an antimalarial drug. Appl Microbiol Biotechnol 72:11–20

    Article  PubMed  CAS  Google Scholar 

  • Lotem J, Sachs L (1996) Control of apoptosis in hematopoiesis and leukemia by cytokines, tumor suppressor and oncogenes. Leukemia 10:925–931

    PubMed  CAS  Google Scholar 

  • Martin VJ, Pitera DJ, Withers ST, Newman JD, Keasling JD (2003) Engineering a mevalonate pathway in Escherichia coli for production of terpenoids. Nat Biotechnol 21:796–802

    Article  PubMed  CAS  Google Scholar 

  • McCarty MF (2003) Turning an ‘Achilles’ Heel’ into an asset–activation of HIF-1alpha during angiostatic therapy will increase tumor sensitivity to iron-catalyzed oxidative damage. Med Hypotheses 61:509–511

    Article  PubMed  CAS  Google Scholar 

  • McColl BK, Loughran SJ, Davydova N, Stacker SA, Achen MG (2005) Mechanisms of lymphangiogenesis: targets for blocking the metastatic spread of cancer. Curr Cancer Drug Targets 5:561–571

    Article  PubMed  CAS  Google Scholar 

  • McCubrey JA, Steelman LS, Chappell WH, Abrams SL, Wong EW, Chang F, Lehmann B, Terrian DM, Milella M, Tafuri A, Stivala F, Libra M, Basecke J, Evangelisti C, Martelli AM, Franklin RA (2007) Roles of the Raf/MEK/ERK pathway in cell growth, malignant transformation and drug resistance. Biochim Biophys Acta 1773:1263–1284

    Article  PubMed  CAS  Google Scholar 

  • Mercer AE, Copple IM, Maggs JL, O’Neill PM, Park BK (2011) The role of heme and the mitochondrion in the chemical and molecular mechanisms of mammalian cell death induced by the artemisinin antimalarials. J Biol Chem 286:987–996

    Article  PubMed  CAS  Google Scholar 

  • Moore JC, Lai H, Li JR, Ren RL, McDougall JA, Singh NP, Chou CK (1995) Oral administration of dihydroartemisinin and ferrous sulfate retarded implanted fibrosarcoma growth in the rat. Cancer Lett 98:83–87

    PubMed  CAS  Google Scholar 

  • Mu D, Chen W, Yu B, Zhang C, Zhang Y, Qi H (2007) Calcium and survivin are involved in the induction of apoptosis by dihydroartemisinin in human lung cancer SPC-A-1 cells. Methods Find Exp Clin Pharmacol 29:33–38

    Article  PubMed  CAS  Google Scholar 

  • Mu D, Zhang W, Chu D, Liu T, Xie Y, Fu E, Jin F (2008) The role of calcium, P38 MAPK in dihydroartemisinin-induced apoptosis of lung cancer PC-14 cells. Cancer Chemother Pharmacol 61:639–645

    Article  PubMed  CAS  Google Scholar 

  • Mukanganyama S, Widersten M, Naik YS, Mannervik B, Hasler JA (2002) Inhibition of glutathione S-transferases by antimalarial drugs possible implications for circumventing anticancer drug resistance. Int J Cancer 97:700–705

    Article  PubMed  CAS  Google Scholar 

  • Nair MS, Acton N, Klayman DL, Kendrick K, Basile DV, Mante S (1986) Production of artemisinin in tissue cultures of Artemisia annua. J Nat Prod 49:504–507

    Article  PubMed  CAS  Google Scholar 

  • Nakase I, Lai H, Singh NP, Sasaki T (2008) Anticancer properties of artemisinin derivatives and their targeted delivery by transferrin conjugation. Int J Pharm 354:28–33

    Article  PubMed  CAS  Google Scholar 

  • Nakase I, Gallis B, Takatani-Nakase T, Oh S, Lacoste E, Singh NP, Goodlett DR, Tanaka S, Futaki S, Lai H, Sasaki T (2009) Transferrin receptor-dependent cytotoxicity of artemisinin-transferrin conjugates on prostate cancer cells and induction of apoptosis. Cancer Lett 274:290–298

    Article  PubMed  CAS  Google Scholar 

  • Nam W, Tak J, Ryu JK, Jung M, Yook JI, Kim HJ, Cha IH (2007) Effects of artemisinin and its derivatives on growth inhibition and apoptosis of oral cancer cells. Head Neck 29:335–340

    Article  PubMed  Google Scholar 

  • Navolanic PM, Steelman LS, McCubrey JA (2003) EGFR family signaling and its association with breast cancer development and resistance to chemotherapy (review). Int J Oncol 22 :237–252

    PubMed  CAS  Google Scholar 

  • Newman JD, Marshall J, Chang M, Nowroozi F, Paradise E, Pitera D, Newman KL, Keasling JD (2006) High-level production of amorpha-4,11-diene in a two-phase partitioning bioreactor of metabolically engineered Escherichia coli. Biotechnol Bioeng 95:684–691

    Article  PubMed  CAS  Google Scholar 

  • Nontprasert A, Pukrittayakamee S, Dondorp AM, Clemens R, Looareesuwan S, White NJ (2002) Neuropathologic toxicity of artemisinin derivatives in a mouse model. Am J Trop Med Hyg 67:423–429

    PubMed  CAS  Google Scholar 

  • Oh S, Jeong IH, Ahn CM, Shin WS, Lee S (2004) Synthesis and antiangiogenic activity of thioacetal artemisinin derivatives. Bioorg Med Chem 12:3783–3790

    Article  PubMed  CAS  Google Scholar 

  • Oh S, Kim BJ, Singh NP, Lai H, Sasaki T (2009) Synthesis and anti-cancer activity of covalent conjugates of artemisinin and a transferrin-receptor targeting peptide. Cancer Lett 274:33–39

    Article  PubMed  CAS  Google Scholar 

  • Panossian LA, Garga NI, Pelletier D (2005) Toxic brainstem encephalopathy after artemisinin treatment for breast cancer. Ann Neurol 58:812–813

    Article  PubMed  Google Scholar 

  • Petras JM, Kyle DE, Gettayacamin M, Young GD, Bauman RA, Webster HK, Corcoran KD, Peggins JO, Vane MA, Brewer TG (1997) Arteether: risks of two-week administration in Macaca mulatta. Am J Trop Med Hyg 56:390–396

    PubMed  CAS  Google Scholar 

  • Petras JM, Young GD, Bauman RA, Kyle DE, Gettayacamin M, Webster HK, Corcoran KD, Peggins JO, Vane MA, Brewer TG (2000) Arteether-induced brain injury in Macaca mulatta. I. The precerebellar nuclei: the lateral reticular nuclei, paramedian reticular nuclei, and perihypoglossal nuclei. Anat Embryol 201:383–397

    Article  PubMed  CAS  Google Scholar 

  • Pommier Y, Sordet O, Antony S, Hayward RL, Kohn KW (2004) Apoptosis defects and chemotherapy resistance: molecular interaction maps and networks. Oncogene 23:2934–2949

    Article  PubMed  CAS  Google Scholar 

  • Reizenstein P (1991) Iron, free radicals and cancer. Med Oncol Tumor Pharmacother 8:229–233

    PubMed  CAS  Google Scholar 

  • Relf M, LeJeune S, Scott PA, Fox S, Smith K, Leek R, Moghaddam A, Whitehouse R, Bicknell R, Harris AL (1997) Expression of the angiogenic factors vascular endothelial cell growth factor, acidic and basic fibroblast growth factor, tumor growth factor beta-1, platelet-derived endothelial cell growth factor, placenta growth factor, and pleiotrophin in human primary breast cancer and its relation to angiogenesis. Cancer Res 57:963–969

    PubMed  CAS  Google Scholar 

  • Reungpatthanaphong P, Mankhetkorn S (2002) Modulation of multidrug resistance by artemisinin, artesunate and dihydroartemisinin in K562/adr and GLC4/adr resistant cell lines. Biol Pharm Bull 25:1555–1561

    Article  PubMed  CAS  Google Scholar 

  • Ribeiro IR, Olliaro P (1998) Safety of artemisinin and its derivatives. A review of published and unpublished clinical trials. Med Trop (Mars) 58:50–53

    CAS  Google Scholar 

  • Riganti C, Doublier S, Costamagna C, Aldieri E, Pescarmona G, Ghigo D, Bosia A (2008) Activation of nuclear factor-kappa B pathway by simvastatin and RhoA silencing increases doxorubicin cytotoxicity in human colon cancer HT29 cells. Mol Pharmacol 74:476–484

    Article  PubMed  CAS  Google Scholar 

  • Riganti C, Doublier S, Viarisio D, Miraglia E, Pescarmona G, Ghigo D, Bosia A (2009) Artemisinin induces doxorubicin resistance in human colon cancer cells via calcium-dependent activation of HIF-1alpha and P-glycoprotein overexpression. Br J Pharmacol 156:1054–1066

    Article  PubMed  CAS  Google Scholar 

  • Ro DK, Paradise EM, Ouellet M, Fisher KJ, Newman KL, Ndungu JM, Ho KA, Eachus RA, Ham TS, Kirby J, Chang MC, Withers ST, Shiba Y, Sarpong R, Keasling JD (2006) Production of the antimalarial drug precursor artemisinic acid in engineered yeast. Nature 440:940–943

    Article  PubMed  CAS  Google Scholar 

  • Segditsas S, Tomlinson I (2006) Colorectal cancer and genetic alterations in the Wnt pathway. Oncogene 25:7531–7537

    Article  PubMed  CAS  Google Scholar 

  • Sertel S, Eichhorn T, Simon CH, Plinkert PK, Johnson SW, Efferth T (2010a) Pharmacogenomic identification of c-Myc/Max-regulated genes associated with cytotoxicity of artesunate towards human colon, ovarian and lung cancer cell lines. Molecules 15:2886–2910

    Article  PubMed  CAS  Google Scholar 

  • Sertel S, Eichhorn T, Sieber S, Sauer A, Weiss J, Plinkert PK, Efferth T (2010b) Factors determining sensitivity or resistance of tumor cell lines towards artesunate. Chem Biol Interact 185:42–52

    Article  PubMed  CAS  Google Scholar 

  • Shaul YD, Seger R (2007) The MEK/ERK cascade: from signaling specificity to diverse functions. Biochim Biophys Acta 1773:1213–1226

    Article  PubMed  CAS  Google Scholar 

  • Shiba Y, Paradise EM, Kirby J, Ro DK, Keasling JD (2007) Engineering of the pyruvate dehydrogenase bypass in Saccharomyces cerevisiae for high-level production of isoprenoids. Metab Eng 9:160–168

    Article  PubMed  CAS  Google Scholar 

  • Shimizu K, Oku N (2004) Cancer anti-angiogenic therapy. Biol Pharm Bull 27:599–605

    Article  PubMed  CAS  Google Scholar 

  • Sieber S, Gdynia G, Roth W, Bonavida B, Efferth T (2009) Combination treatment of malignant B cells using the anti-CD20 antibody rituximab and the anti-malarial artesunate. Int J Oncol 35:149–158

    PubMed  CAS  Google Scholar 

  • Simonsson US, Lindell M, Raffalli-Mathieu F, Lannerbro A, Honkakoski P, Lang MA (2006) In vivo and mechanistic evidence of nuclear receptor CAR induction by artemisinin. Eur J Clin Invest 36:647–653

    Article  PubMed  CAS  Google Scholar 

  • Singh NP, Lai H (2001) Selective toxicity of dihydroartemisinin and holotransferrin toward human breast cancer cells. Life Sci 70:49–56

    Article  PubMed  CAS  Google Scholar 

  • Singh NP, Lai HC (2004) Artemisinin induces apoptosis in human cancer cells. Anticancer Res 24:2277–2280

    PubMed  CAS  Google Scholar 

  • Singh NP, Lai HC (2005) Synergistic cytotoxicity of artemisinin and sodium butyrate on human cancer cells. Anticancer Res 25:4325–4331

    PubMed  CAS  Google Scholar 

  • Singh NP, Panwar VK (2006) Case report of a pituitary macroadenoma treated with artemether. Integr Cancer Ther 5:391–394

    Article  PubMed  Google Scholar 

  • Singh NP, Verma KB (2002) Case report of a laryngeal squamous cell carcinoma treated with artesunate. Arch Oncol 10:279–280

    Article  Google Scholar 

  • Souret FF, Kim Y, Wyslouzil BE, Wobbe KK, Weathers PJ (2003) Scale-up of Artemisia annua L. hairy root cultures produces complex patterns of terpenoid gene expression. Biotechnol Bioeng 83:653–667

    Article  PubMed  CAS  Google Scholar 

  • Steinbrück L, Pereira G, Efferth T (2010) Effects of artesunate on cytokinesis and G2/M cell cycle progression of tumour cells and budding yeast. Cancer Genomics Proteomics 7:337–346

    PubMed  Google Scholar 

  • Stepniewska K, Day N, Babiker A, Lalloo D, Warrell D, Olliaro P, White N (2001) A meta-analysis using individual patient data of trials comparing artemether with quinine in the treatment of severe falciparum malaria. Trans R Soc Trop Med Hyg 95:637–650

    Article  CAS  Google Scholar 

  • Sukhija M, Medhi B, Pandhi P (2006) Effects of artemisinin, artemether, arteether on the pharmacokinetics of carbamazepine. Pharmacology 76:110–116

    Article  PubMed  CAS  Google Scholar 

  • Sundar SN, Marconett CN, Doan VB, Willoughby JA Sr, Firestone GL (2008) Artemisinin selectively decreases functional levels of estrogen receptor-alpha and ablates estrogen-induced proliferation in human breast cancer cells. Carcinogenesis 29:2252–2258

    Article  PubMed  CAS  Google Scholar 

  • Svensson US, Ashton M (1999) Identification of the human cytochrome P450 enzymes involved in the in vitro metabolism of artemisinin. Br J Clin Pharmacol 48:528–535

    Article  PubMed  CAS  Google Scholar 

  • Svensson US, Maki-Jouppila M, Hoffmann KJ, Ashton M (2003) Characterisation of the human liver in vitro metabolic pattern of artemisinin and auto-induction in the rat by use of nonlinear mixed effects modelling. Biopharm Drug Dispos 24:71–85

    Article  PubMed  CAS  Google Scholar 

  • Sweeney CJ, Mehrotra S, Sadaria MR, Kumar S, Shortle NH, Roman Y, Sheridan C, Campbell RA, Murry DJ, Badve S, Nakshatri H (2005) The sesquiterpene lactone parthenolide in combination with docetaxel reduces metastasis and improves survival in a xenograft model of breast cancer. Mol Cancer Ther 4:1004–1012

    Article  PubMed  CAS  Google Scholar 

  • Taketani S, Kakimoto K, Ueta H, Masaki R, Furukawa T (2003) Involvement of ABC7 in the biosynthesis of heme in erythroid cells: interaction of ABC7 with ferrochelatase. Blood 101:3274–3280

    Article  PubMed  CAS  Google Scholar 

  • Tan RX, Zheng WF, Tang HQ (1998) Biologically active substances from the genus Artemisia. Planta Med 64:295–302

    Article  PubMed  CAS  Google Scholar 

  • Tin AS, Sundar SN, Tran KQ, Park AH, Poindexter KM, Firestone GL (2012) Antiproliferative effects of artemisinin on human breast cancer cells requires the downregulated expression of the E2F1 transcription factor and loss of E2F1-target cell cycle genes. Anticancer Drugs 23(4):370–379

    Article  PubMed  CAS  Google Scholar 

  • Toovey S (2006) Are currently deployed artemisinins neurotoxic? Toxicol Lett 166:95–104

    Article  PubMed  CAS  Google Scholar 

  • Toovey S, Jamieson A (2004) Audiometric changes associated with the treatment of uncomplicated falciparum malaria with co-artemether. Trans R Soc Trop Med Hyg 98:261–267, discussion 268–269

    Article  PubMed  Google Scholar 

  • Tu Y (1999) The development of new antimalarial drugs: qinghaosu and dihydro-qinghaosu. Chin Med J (Engl) 112:976–977

    CAS  Google Scholar 

  • Tuttle TM (2004) Technical advances in sentinel lymph node biopsy for breast cancer. Am Surg 70:407–413

    PubMed  Google Scholar 

  • van Agtmael MA, Eggelte TA, van Boxtel CJ (1999) Artemisinin drugs in the treatment of malaria: from medicinal herb to registered medication. Trends Pharmacol Sci 20:199–205

    Article  PubMed  Google Scholar 

  • Van Geldre E, Vergauwe A, Van den Eeckhout E (1997) State of the art of the production of the antimalarial compound artemisinin in plants. Plant Mol Biol 33:199–209

    Article  PubMed  Google Scholar 

  • van Hensbroek MB, Onyiorah E, Jaffar S, Schneider G, Palmer A, Frenkel J, Enwere G, Forck S, Nusmeijer A, Bennett S, Greenwood B, Kwiatkowski D (1996) A trial of artemether or quinine in children with cerebral malaria. N Engl J Med 335:69–75

    Article  PubMed  Google Scholar 

  • Volm M, Kastel M, Mattern J, Efferth T (1993) Expression of resistance factors (P-glycoprotein, glutathione S-transferase-pi, and topoisomerase II) and their interrelationship to proto-oncogene products in renal cell carcinomas. Cancer 71:3981–3987

    Article  PubMed  CAS  Google Scholar 

  • Volm M, Koomagi R, Mattern J, Efferth T (2002a) Expression profile of genes in non-small cell lung carcinomas from long-term surviving patients. Clin Cancer Res 8:1843–1848

    PubMed  CAS  Google Scholar 

  • Volm M, Koomagi R, Mattern J, Efferth T (2002b) Protein expression profiles indicative for drug resistance of non-small cell lung cancer. Br J Cancer 87:251–257

    Article  PubMed  CAS  Google Scholar 

  • Wang CW (1961) The forests of China, with a survey of grassland and desert vegetation, vol 5. Harvard University, Maria Moors Cabot Foundation, Cambridge, MA, pp 171–187

    Google Scholar 

  • Wang J, Guo Y, Zhang BC, Chen ZT, Gao JF (2007a) Induction of apoptosis and inhibition of cell migration and tube-like formation by dihydroartemisinin in murine lymphatic endothelial cells. Pharmacology 80:207–218

    Article  PubMed  CAS  Google Scholar 

  • Wang JX, Tang W, Yang ZS, Wan J, Shi LP, Zhang Y, Zhou R, Ni J, Hou LF, Zhou Y, He PL, Yang YF, Li Y, Zuo JP (2007b) Suppressive effect of a novel water-soluble artemisinin derivative SM905 on T cell activation and proliferation in vitro and in vivo. Eur J Pharmacol 564:211–218

    Article  PubMed  CAS  Google Scholar 

  • Wang JX, Tang W, Shi LP, Wan J, Zhou R, Ni J, Fu YF, Yang YF, Li Y, Zuo JP (2007c) Investigation of the immunosuppressive activity of artemether on T-cell activation and proliferation. Br J Pharmacol 150:652–661

    Article  PubMed  CAS  Google Scholar 

  • Wang J, Zhang B, Guo Y, Li G, Xie Q, Zhu B, Gao J, Chen Z (2008) Artemisinin inhibits tumor lymphangiogenesis by suppression of vascular endothelial growth factor C. Pharmacology 82:148–155

    Article  PubMed  CAS  Google Scholar 

  • Wartenberg M, Wolf S, Budde P, Grunheck F, Acker H, Hescheler J, Wartenberg G, Sauer H (2003) The antimalaria agent artemisinin exerts antiangiogenic effects in mouse embryonic stem cell-derived embryoid bodies. Lab Invest 83:1647–1655

    Article  PubMed  CAS  Google Scholar 

  • Weifeng T, Feng S, Xiangji L, Changqing S, Zhiquan Q, Huazhong Z, Peining Y, Yong Y, Mengchao W, Xiaoqing J, Wan-Yee L (2011) Artemisinin inhibits in vitro and in vivo invasion and metastasis of human hepatocellular carcinoma cells. Phytomedicine 18:58–62

    Article  CAS  Google Scholar 

  • White NJ (2008) Qinghaosu (artemisinin): the price of success. Science 320:330–334

    Article  PubMed  CAS  Google Scholar 

  • Willoughby JA Sr, Sundar SN, Cheung M, Tin AS, Modiano J, Firestone GL (2009) Artemisinin blocks prostate cancer growth and cell cycle progression by disrupting Sp1 interactions with the cyclin-dependent kinase-4 (CDK4) promoter and inhibiting CDK4 gene expression. J Biol Chem 284:2203–2213

    Article  PubMed  CAS  Google Scholar 

  • Woerdenbag HJ, Moskal TA, Pras N, Malingre TM, el-Feraly FS, Kampinga HH, Konings AW (1993) Cytotoxicity of artemisinin-related endoperoxides to Ehrlich ascites tumor cells. J Nat Prod 56:849–856

    Article  PubMed  CAS  Google Scholar 

  • Woodrow CJ, Haynes RK, Krishna S (2005) Artemisinins. Postgrad Med J 81:71–78

    Article  PubMed  CAS  Google Scholar 

  • Wouters BG, van den Beucken T, Magagnin MG, Lambin P, Koumenis C (2004) Targeting hypoxia tolerance in cancer. Drug Resist Updat 7:25–40

    Article  PubMed  CAS  Google Scholar 

  • Wu XH, Zhou HJ, Lee J (2006) 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. Anticancer Drugs 17:839–848

    Article  PubMed  CAS  Google Scholar 

  • Wu J, Hu D, Yang G, Zhou J, Yang C, Gao Y, Zhu Z (2011) Down-regulation of BMI-1 cooperates with artemisinin on growth inhibition of nasopharyngeal carcinoma cells. J Cell Biochem 112:1938–1948

    Article  PubMed  CAS  Google Scholar 

  • Yamachika E, Habte T, Oda D (2004) Artemisinin: an alternative treatment for oral squamous cell carcinoma. Anticancer Res 24:2153–2160

    PubMed  CAS  Google Scholar 

  • Yeung S, Pongtavornpinyo W, Hastings IM, Mills AJ, White NJ (2004) Antimalarial drug resistance, artemisinin-based combination therapy, and the contribution of modeling to elucidating policy choices. Am J Trop Med Hyg 71:179–186

    PubMed  Google Scholar 

  • Yu JL, Coomber BL, Kerbel RS (2002) A paradigm for therapy-induced microenvironmental changes in solid tumors leading to drug resistance. Differentiation 70:599–609

    Article  PubMed  Google Scholar 

  • Zhang ZY, Yu SQ, Miao LY, Huang XY, Zhang XP, Zhu YP, Xia XH, Li DQ (2008) Artesunate combined with vinorelbine plus cisplatin in treatment of advanced non-small cell lung cancer: a randomized controlled trial. Zhong Xi Yi Jie He Xue Bao 6:134–138

    Article  PubMed  CAS  Google Scholar 

  • Zhao Y, Jiang W, Li B, Yao Q, Dong J, Cen Y, Pan X, Li J, Zheng J, Pang X, Zhou H (2011) Artesunate enhances radiosensitivity of human non-small cell lung cancer A549 cells via increasing NO production to induce cell cycle arrest at G(2)/M phase. Int Immunopharmacol 11:2039–2046

    Article  PubMed  CAS  Google Scholar 

  • Zhou HJ, Wang WQ, Wu GD, Lee J, Li A (2007) Artesunate inhibits angiogenesis and downregulates vascular endothelial growth factor expression in chronic myeloid leukemia K562 cells. Vascul Pharmacol 47:131–138

    Article  PubMed  CAS  Google Scholar 

  • Zhou HJ, Wang Z, Li A (2008) Dihydroartemisinin induces apoptosis in human leukemia cells HL60 via downregulation of transferrin receptor expression. Anticancer Drugs 19:247–255

    Article  PubMed  Google Scholar 

Download references

Acknowledgments

We thank Dr. Herwig Jansen (Dafra, Turnhout, Belgium) for providing information about the biosynthesis of artemisinin from chicory.

Author information

Authors and Affiliations

  1. Department of Otorhinolaryngology, Head and Neck Surgery, University Heidelberg, Im Neuenheimer Feld 400, 69120, Heidelberg, Germany

    Serkan Sertel & Peter K. Plinkert

  2. Department of Pharmaceutical Biology, Institute of Pharmacy and Biochemistry, Johannes Gutenberg University, Staudinger Weg 5, 55128, Mainz, Germany

    Thomas Efferth

Authors
  1. Serkan Sertel
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Peter K. Plinkert
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Thomas Efferth
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Thomas Efferth .

Editor information

Editors and Affiliations

  1. Center of Pharma Research, Department of Pharmacy, Ludwig-Maximillians-University, Butenandtstr. 5, Munich, 81377, Germany

    Hildebert Wagner

  2. , Rheinische Friedrich-Wilhelms-University, Medical Policlinic/Medical Clinic III, Wilhelmstrasse 35-37, Bonn, 53111, Germany

    Gudrun Ulrich-Merzenich

Rights and permissions

Reprints and permissions

Copyright information

© 2013 Springer-Verlag Wien

About this chapter

Cite this chapter

Sertel, S., Plinkert, P.K., Efferth, T. (2013). Activity of Artemisinin-Type Compounds Against Cancer Cells. In: Wagner, H., Ulrich-Merzenich, G. (eds) Evidence and Rational Based Research on Chinese Drugs. Springer, Vienna. https://doi.org/10.1007/978-3-7091-0442-2_8

Download citation

  • DOI: https://doi.org/10.1007/978-3-7091-0442-2_8

  • Published:

  • Publisher Name: Springer, Vienna

  • Print ISBN: 978-3-7091-0441-5

  • Online ISBN: 978-3-7091-0442-2

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics

Search

Navigation