The anti-malarial artesunate is also active against cancer

Publication type:
Journal article
Metadata:
Autoren
  • T Efferth
  • H Dunstan
  • A Sauerbrey
  • H Miyachi
  • CR Chitambar
Autoren-URL
https://www.webofscience.com/api/gateway?GWVersion=2&SrcApp=fis-test-1&SrcAuth=WosAPI&KeyUT=WOS:000167628200013&DestLinkType=FullRecord&DestApp=WOS_CPL
Externe Identifier
  • Clarivate Analytics Document Solution ID: 413TN
  • PubMed Identifier: 11251172
ISSN
1019-6439
Ausgabe der Veröffentlichung
4
Zeitschrift
INTERNATIONAL JOURNAL OF ONCOLOGY
Schlüsselwörter
  • BUB3
  • chemotherapy
  • CLN2
  • drug resistance
  • neoplasms
  • Saccharomyces cerevisiae mutant strains
Paginierung
767 - 773
Datum der Veröffentlichung
2001
Status
Published
Titel
The anti-malarial artesunate is also active against cancer
Sub types
  • Article
Ausgabe der Zeitschrift
18

Data source: Web of Science (Lite)

Other metadata sources:
Autoren
  • Thomas Efferth
  • Heather Dunstan
  • Axel Sauerbrey
  • Hayato Miyachi
  • Christopher Chitambar
DOI
10.3892/ijo.18.4.767
eISSN
1791-2423
ISSN
1019-6439
Zeitschrift
International Journal of Oncology
Online publication date
2001
Status
Published online
Herausgeber
Spandidos Publications
Herausgeber URL
http://dx.doi.org/10.3892/ijo.18.4.767
Datum der Datenerfassung
2017
Titel
The anti-malarial artesunate is also active against cancer

Data source: Crossref

Abstract
Artesunate (ART) is a semi-synthetic derivative of artemisinin, the active principle of the Chinese herb Artemisia annua. ART reveals remarkable activity against otherwise multidrug-resistant Plasmodium falciparum and P. vivax malaria. ART has now been analyzed for its anti-cancer activity against 55 cell lines of the Developmental Therapeutics Program of the National Cancer Institute, USA. ART was most active against leukemia and colon cancer cell lines (mean GI50 values: 1.11+/-0.56 microM and 2.13+/-0.74 microM , respectively). Non-small cell lung cancer cell lines showed the highest mean GI50 value (25.62+/-14.95 microM) indicating the lowest sensitivity towards ART in this test panel. Intermediate GI50 values were obtained for melanomas, breast, ovarian, prostate, CNS, and renal cancer cell lines. Importantly, a comparison of ART's cytotoxicity with those of other standard cytostatic drugs showed that ART was active in molar ranges comparable to those of established anti-tumor drugs. Furthermore, we tested CEM leukemia sub-lines resistant to either doxorubicin, vincristine, methotrexate, or hydroxyurea which do not belong to the N.C.I. screening panel. None of these drug-resistant cell lines showed cross resistance to ART. To gain insight into the molecular mechanisms of ART's cytotoxicity, we used a panel of isogenic Saccaromyces cerevisiae strains with defined genetic mutations in DNA repair, DNA checkpoint and cell proliferation genes. A yeast strain with a defective mitosis regulating BUB3 gene showed increased ART sensitivity and another strain with a defective proliferation-regulating CLN2 gene showed increased ART resistance over the wild-type strain, wt644. None of the other DNA repair or DNA check-point deficient isogenic strains were different from the wild-type. These results and the known low toxicity of ART are clues that ART may be a promising novel candidate for cancer chemotherapy.
Addresses
  • Virtual Campus Rhineland-Palatinate, P.O. Box 4380, D-55033 Mainz, Germany. efferth@vcrp.de
Autoren
  • T Efferth
  • H Dunstan
  • A Sauerbrey
  • H Miyachi
  • CR Chitambar
DOI
10.3892/ijo.18.4.767
eISSN
1791-2423
Externe Identifier
  • PubMed Identifier: 11251172
Open access
false
ISSN
1019-6439
Ausgabe der Veröffentlichung
4
Zeitschrift
International journal of oncology
Schlüsselwörter
  • Tumor Cells, Cultured
  • Humans
  • Saccharomyces cerevisiae
  • Neoplasms
  • Leukemia
  • Sesquiterpenes
  • Artemisinins
  • Rhodamines
  • Cyclins
  • Proteins
  • Cell Cycle Proteins
  • Saccharomyces cerevisiae Proteins
  • Antineoplastic Agents
  • Antimalarials
  • Fluorescent Dyes
  • Drug Screening Assays, Antitumor
  • Cell Division
  • Drug Resistance, Neoplasm
  • Cyclin G
  • Cyclin G1
  • Poly-ADP-Ribose Binding Proteins
  • Artesunate
  • Tripeptidyl-Peptidase 1
Sprache
eng
Medium
Print
Paginierung
767 - 773
Datum der Veröffentlichung
2001
Status
Published
Datum der Datenerfassung
2001
Titel
The anti-malarial artesunate is also active against cancer.
Sub types
  • Comparative Study
  • Journal Article
Ausgabe der Zeitschrift
18

Data source: Europe PubMed Central

Abstract
Artesunate (ART) is a semi-synthetic derivative of artemisinin, the active principle of the Chinese herb Artemisia annua. ART reveals remarkable activity against otherwise multidrug-resistant Plasmodium falciparum and P. vivax malaria. ART has now been analyzed for its anti-cancer activity against 55 cell lines of the Developmental Therapeutics Program of the National Cancer Institute, USA. ART was most active against leukemia and colon cancer cell lines (mean GI50 values: 1.11+/-0.56 microM and 2.13+/-0.74 microM , respectively). Non-small cell lung cancer cell lines showed the highest mean GI50 value (25.62+/-14.95 microM) indicating the lowest sensitivity towards ART in this test panel. Intermediate GI50 values were obtained for melanomas, breast, ovarian, prostate, CNS, and renal cancer cell lines. Importantly, a comparison of ART's cytotoxicity with those of other standard cytostatic drugs showed that ART was active in molar ranges comparable to those of established anti-tumor drugs. Furthermore, we tested CEM leukemia sub-lines resistant to either doxorubicin, vincristine, methotrexate, or hydroxyurea which do not belong to the N.C.I. screening panel. None of these drug-resistant cell lines showed cross resistance to ART. To gain insight into the molecular mechanisms of ART's cytotoxicity, we used a panel of isogenic Saccaromyces cerevisiae strains with defined genetic mutations in DNA repair, DNA checkpoint and cell proliferation genes. A yeast strain with a defective mitosis regulating BUB3 gene showed increased ART sensitivity and another strain with a defective proliferation-regulating CLN2 gene showed increased ART resistance over the wild-type strain, wt644. None of the other DNA repair or DNA check-point deficient isogenic strains were different from the wild-type. These results and the known low toxicity of ART are clues that ART may be a promising novel candidate for cancer chemotherapy.
Autoren
  • T Efferth
  • H Dunstan
  • A Sauerbrey
  • H Miyachi
  • CR Chitambar
Autoren-URL
https://www.ncbi.nlm.nih.gov/pubmed/11251172
DOI
10.3892/ijo.18.4.767
ISSN
1019-6439
Ausgabe der Veröffentlichung
4
Zeitschrift
Int J Oncol
Schlüsselwörter
  • Antimalarials
  • Antineoplastic Agents
  • Artemisinins
  • Artesunate
  • Cell Cycle Proteins
  • Cell Division
  • Cyclin G
  • Cyclin G1
  • Cyclins
  • Drug Resistance, Neoplasm
  • Drug Screening Assays, Antitumor
  • Fluorescent Dyes
  • Humans
  • Leukemia
  • Neoplasms
  • Poly-ADP-Ribose Binding Proteins
  • Proteins
  • Rhodamines
  • Saccharomyces cerevisiae
  • Saccharomyces cerevisiae Proteins
  • Sesquiterpenes
  • Tripeptidyl-Peptidase 1
  • Tumor Cells, Cultured
Sprache
eng
Country
Greece
Paginierung
767 - 773
Datum der Veröffentlichung
2001
Status
Published
Datum, an dem der Datensatz öffentlich gemacht wurde
2001
Titel
The anti-malarial artesunate is also active against cancer.
Sub types
  • Comparative Study
  • Journal Article
Ausgabe der Zeitschrift
18

Data source: PubMed

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