Download PDF
Zeitschrift für Komplementärmedizin 2023; 15(06): 84-89
DOI: 10.1055/a-2188-2050
Wissen
Artemisia und Artesunate

Artemisia annua und Artesunate in der Onkologie

Thomas Efferth
› Further Information
    Permissions and Reprints

Summary

Artesunate ist ein klinisch etabliertes Medikament zur Malariabehandlung. Präklinische Daten weisen darauf hin, dass Artesunate und Artemisinin, die Leitsubstanz aus der chinesischen Heilpflanze Artemisia annua L., auch gegen Krebs eingesetzt werden könnten.

Im Allgemeinen wurden Artemisinin und Artesunate nach den bisher vorliegenden klinischen Befunden gut vertragen, wobei vereinzelt immer wieder auch signifikante Nebenwirkungen wie Hämatotoxizität, Hepatotoxizität oder Neurotoxizität auftraten. Auf das Vorkommen schwerer Nebenwirkungen muss auch weiterhin besonderes Augenmerk gelegt werden, insbesondere wenn Artesunate zusammen mit anderen Medikamenten verabreicht wird.

Die veterinärmedizinischen Studien zeigen, dass spontane Tiertumoren nicht nur ein interessantes Modell für in der Translation präklinischer Daten in die Klinik sind, sondern dass Artesunate- und Artemisia-annua-Präparate eine neue Behandlungsoption für Haustiere mit Tumorerkrankungen darstellen könnten.

Die Wirksamkeit von Artesunate gegen verschiedene solide humane Tumoren ist bisher als eher mäßig einzustufen, wobei das Zervixkarzinom möglicherweise besser anzusprechen scheint. Insgesamt liegen noch zu wenige Daten vor, um die klinischen Ansprechraten bei verschiedenen Tumortypen zuverlässig beantworten zu können. Weitere größere klinische Phase-II- und -III-Studien sind nötig.

Keywords

Chemotherapie - Molekulare Pharmakologie - Naturstoffe - Rationale Phytotherapie - Sesquiterpenoide - Traditionelle Chinesische Medizin


Publication History

Article published online:
12 December 2023

© 2023. Thieme. All rights reserved.

© Karl F. Haug Verlag in MVS Medizinverlage Stuttgart GmbH & Co.
KG

 

  • Literatur

  • 1 Tu YY, Ni MY, Zhong YR. et al Studies on the constituents of artemisia annua L (author’s transl). Yao Xue Xue Bao 1981; 16: 366-370
    PubMedSearch in Google Scholar
  • 2 Jeremic D, Jokic A, Behbud A. et al New type of sesquiterpene lactones isolated from artemisia annua L. arteannuin B. Tetrahedron Lett 1973; 14: 3039-3042
    CrossrefSearch in Google Scholar
  • 3 Tu YY. The constituents of young artemisia annua. Zhong Yao Tong Bao. 1985 35–36 18
    PubMedSearch in Google Scholar
  • 4 Tu YY. Artemisinin – A gift from traditional Chinese medicine to the world (nobel lecture). Angew Chem Int Ed Engl 2016; 55: 10210-10226
    CrossrefPubMedSearch in Google Scholar
  • 5 Ginsburg H, Atamna H. The redox status of malaria-infected erythrocytes: An overview with an emphasis on unresolved problems. Parasite 1994; 01: 5-13
    CrossrefPubMedSearch in Google Scholar
  • 6 Shenai BR, Sijwali PS, Singh A. et al Characterization of native and recombinant falcipain-2, a principal trophozoite cysteine protease and essential hemoglobinase of plasmodium falciparum. J Biol Chem 2000; 275: 29000-29010
    CrossrefPubMedSearch in Google Scholar
  • 7 O’Neill PM, Posner GH. A medicinal chemistry perspective on artemisinin and related endoperoxides. J Med Chem 2004; 47: 2945-2964
    CrossrefPubMedSearch in Google Scholar
  • 8 Loo CS, Lam NS, Yu D. et al Artemisinin and its derivatives in treating protozoan infections beyond malaria. Pharmacol Res 2017; 117: 192-217
    CrossrefPubMedSearch in Google Scholar
  • 9 Naß J, Efferth T. The activity of artemisia spp. and their constituents against trypanosomiasis. Phytomedicine 2018; 47: 184-191
    CrossrefPubMedSearch in Google Scholar
  • 10 Pérez del Villar L, Burguillo FJ, López-Abán J. et al Systematic review and meta-analysis of artemisinin based therapies for the treatment and prevention of schistosomiasis. PLoS One 2012; 07 (09) e45867
    CrossrefPubMedSearch in Google Scholar
  • 11 Saeed MEM, Krishna S, Greten HJ. et al Antischistosomal activity of artemisinin derivatives in vivo and in patients. Pharmacol Res 2016; 110: 216-226
    CrossrefPubMedSearch in Google Scholar
  • 12 Efferth T, Romero MR, Wolf DG. et al The antiviral activities of artemisinin and artesunate. Clin Infect Dis 2008; 47: 804-811
    CrossrefPubMedSearch in Google Scholar
  • 13 Efferth T. Beyond malaria: The inhibition of viruses by artemisinin-type compounds. Biotechnol Adv 2018; 36: 1730-1737
    CrossrefPubMedSearch in Google Scholar
  • 14 Efferth T, Oesch F. The immunosuppressive activity of artemisinin-type drugs towards inflammatory and autoimmune diseases. Med Res Rev 2021; 41: 3023-3061
    CrossrefPubMedSearch in Google Scholar
  • 15 Wu T, Feng H, He M. et al Efficacy of artemisinin and its derivatives in animal models of type 2 diabetes mellitus: A systematic review and meta-analysis. Pharmacol Res 2022; 175: 105994
    CrossrefPubMedSearch in Google Scholar
  • 16 Efferth T, Rücker G, Falkenberg M. et al Detection of apoptosis in KG-1a leukemic cells treated with investigational drugs. Arzneimittelforschung 1996; 46: 196-200
    PubMedSearch in Google Scholar
  • 17 Efferth T. From ancient herb to modern drug: Artemisia annua and artemisinin for cancer therapy. Semin Cancer Biol 2017; 46: 65-83
    CrossrefPubMedSearch in Google Scholar
  • 18 Kwon JY, Moskwa N, Kang W. et al Canine as a comparative and translational model for human mammary tumor. J Breast Cancer 2023; 26: 1-13
    CrossrefPubMedSearch in Google Scholar
  • 19 Rutteman GR, Erich SA, Mol JA. et al Safety and efficacy field study of artesunate for dogs with non-resectable tumours. Anticancer Res 2013; 33: 1819-1827
    PubMedSearch in Google Scholar
  • 20 Hosoya K, Couto CG, London CA. et al Comparison of high-dose intermittent and low-dose continuous oral artemisinin in dogs with naturally occurring tumors. J Am Anim Hosp Assoc 2014; 50: 390-395
    CrossrefPubMedSearch in Google Scholar
  • 21 Breuer E, Efferth T. Treatment of iron-loaded veterinary sarcoma by artemisia annua. Nat Prod Bioprospect 2014; 04: 113-118
    CrossrefPubMedSearch in Google Scholar
  • 22 Saeed MEM, Breuer E, Hegazy MF. et al Retrospective study of small pet tumors treated with artemisia annua and iron. Int J Oncol 2020; 56: 123-138
    CrossrefPubMedSearch in Google Scholar
  • 23 Singh NP, Verma KB. Case report of a laryngeal squamous cell carcinoma treated with artesunate. Arch Oncol 2002; 10: 279-280
    CrossrefSearch in Google Scholar
  • 24 Berger TG, Dieckmann D, Efferth T. et al Artesunate in the treatment of metastatic uveal melanoma – first experiences. Oncol Rep 2005; 14: 1599-1603
    PubMedSearch in Google Scholar
  • 25 Michaelsen FW, Saeed ME, Schwarzkopf J. et al Activity of artemisia annua and artemisinin derivatives, in prostate carcinoma. Phytomedicine 2015; 22: 1223-1231
    CrossrefPubMedSearch in Google Scholar
  • 26 Efferth T, Schöttler U, Krishna S. et al Hepatotoxicity by combination treatment of temozolomide, artesunate and chinese herbs in a glioblastoma multiforme patient: case report review of the literature. Arch Toxicol 2017; 91: 1833-1846
    CrossrefPubMedSearch in Google Scholar
  • 27 Uhl M, Schwab S, Efferth T. Fatal liver and bone marrow toxicity by combination treatment of dichloroacetate and artesunate in a glioblastoma multiforme patient: Case report and review of the literature. Front Oncol 2016; 06: 204
    CrossrefPubMedSearch in Google Scholar
  • 28 Panossian LA, Garga NI, Pelletier D. Toxic brainstem encephalopathy after artemisinin treatment for breast cancer. Ann Neurol 2005; 58: 812-813
    CrossrefPubMedSearch in Google Scholar
  • 29 White NJ, Ashley EA, Nosten F. Toxic brainstem encephalopathy after artemisinin treatment for breast cancer. Ann Neurol 2006; 59: 725-726
    CrossrefPubMedSearch in Google Scholar
  • 30 Ericsson T, Sundell J, Torkelsson A. et al Effects of artemisinin antimalarials on cytochrome P450 enzymes in vitro using recombinant enzymes and human liver microsomes: Potential implications for combination therapies. Xenobiotica 2014; 44: 615-626
    CrossrefPubMedSearch in Google Scholar
  • 31 Veerappan A, Eichhorn T, Zeino M. et al Differential interactions of the broad spectrum drugs artemisinin, dihydroartemisinin and artesunate with serum albumin. Phytomedicine 2013; 20: 969-974
    CrossrefPubMedSearch in Google Scholar
  • 32 König M, von Hagens C, Hoth S. et al Investigation of ototoxicity of artesunate as add-on therapy in patients with metastatic or locally advanced breast cancer: New audiological results from a prospective, open, uncontrolled, monocentric phase I study. Cancer Chemother Pharmacol 2016; 77: 413-427
    CrossrefPubMedSearch in Google Scholar
  • 33 von Hagens C, Walter-Sack I, Goeckenjan M. et al Prospective open uncontrolled phase I study to define a well-tolerated dose of oral artesunate as add-on therapy in patients with metastatic breast cancer (ARTIC M33/2). Breast Cancer Res Treat 2017; 164: 359-369
    CrossrefPubMedSearch in Google Scholar
  • 34 von Hagens C, Walter-Sack I, Goeckenjan M. et al Long-term add-on therapy (compassionate use) with oral artesunate in patients with metastatic breast cancer after participating in a phase I study (ARTIC M33/2). Phytomedicine 2019; 54: 140-148
    CrossrefPubMedSearch in Google Scholar
  • 35 Deeken JF, Wang H, Hartley M. et al A phase I study of intravenous artesunate in patients with advanced solid tumor malignancies. Cancer Chemother Pharmacol 2018; 81: 587-596
    CrossrefPubMedSearch in Google Scholar
  • 36 Trimble CL, Levinson K, Maldonado L. et al A first-in-human proof-of-concept trial of intravaginal artesunate to treat cervical intraepithelial neoplasia 2/3 (CIN2/3). Gynecol Oncol 2020; 157: 188-194
    CrossrefPubMedSearch in Google Scholar
  • 37 Jansen FH, Adoubi I, Kouassi Comoe JC. et al First study of oral artenimol-r in advanced cervical cancer: Clinical benefit, tolerability and tumor markers. Anticancer Res 2011; 31: 4417-4422
    PubMedSearch in Google Scholar
  • 38 Saeed MEM, Cives-Losada C, Efferth T. Biomarker expression profiling in cervix carcinoma biopsies unravels WT1 as a target of artesunate. Cancer Genomics Proteomics 2022; 19: 727-739
    CrossrefPubMedSearch in Google Scholar
  • 39 Zhang ZY, Yu SQ, Miao LY. et al 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 2008; 06: 134-138
    CrossrefPubMedSearch in Google Scholar
  • 40 Krishna S, Ganapathi S, Ster IC. et al A randomised, double blind, placebo-controlled pilot study of oral artesunate therapy for colorectal cancer. EBioMedicine 2014; 02: 82-90
    CrossrefPubMedSearch in Google Scholar
  • 41 Efferth T, Kaina B. Toxicity of the antimalarial artemisinin and its derivatives. Crit Rev Toxicol 2010; 40: 405-421
    CrossrefPubMedSearch in Google Scholar
  • 42 Efferth T. Cancer combination therapies with artemisinin-type drugs. Biochem Pharmacol 2017; 139: 56-70
    CrossrefPubMedSearch in Google Scholar