The anti-malarial artesunate is also active against cancer

Efferth, Thomas; Dunstan, Heather M.; Sauerbrey, Axel; Miyachi, Hayato; Chitambar, Christopher R.

doi:10.3892/ijo.18.4.767

Cited by 324 publications

(365 citation statements)

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“…It is unknown yet, whether ARS derivatives belong to this category, as its prolonged use has not been reported. However, given its efficacy against drug-resistant tumor cells 17,19 and the relation to antiangiogenesis, it appears to be well-suited for adjuvant therapy in combination with classical chemotherapy. …”

Section: Discussionmentioning

confidence: 99%

“…35 The response of the 60 tumor cell lines to ART has been determined in a previous collaboration with the NCI. 17 The GI 50 values for ART as well as for other ARSs (ARS, arteether (ARE), artemether (ARM), artemisitene (ARTEMIS), arteanuine B (ARAB), dihydroartemisinyl ester stereoisomers 1 and 2 (ARTEST 1 and 2)) have been deposited in the database of the Developmental Therapeutics Program of the NCI (http://dtp.nci.nih.gov) (see Supplementary Table 1).…”

Section: Cell Culturementioning

confidence: 99%

“…14 The observation that ART inhibits the growth of many transformed cell lines has led to the hypothesis that the drug can also be useful for the treatment of human neoplasia. [15][16][17][18][19][20][21][22][23][24] As shown by us and others, [25][26][27][28][29][30][31][32] ARSs reveal antiangiogenic features in vitro and in vivo. The molecular determinants of the antiangiogenic activity of ARSs are incompletely understood at present.…”

Section: Introductionmentioning

confidence: 99%

“…The mRNA expression as determined by microarray analyses has been reported 33 and deposited in the NCI's database (http://dtp.nci.nih.gov). The GI 50 values for ART in 60 cell lines of the NCI have been described by us, 17 while the GI 50 values for the other ARSs have been deposited in the NCI's database. We subjected these data to Kendall's t-test, hierarchical cluster analysis, and cluster image mapping to further characterize mRNA expression profiles of angiogenesis-related genes.…”

Section: Introductionmentioning

confidence: 99%

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Microarray expression profiles of angiogenesis-related genes predict tumor cell response to artemisinins

et al. 2006

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Artemisinin (ARS) and its derivatives are used for the second-line therapy of malaria infections with Plasmodium falciparum and P. vivax. ARSs also reveal profound antitumor activity in vitro and in vivo. In the present investigation, we correlated the mRNA expression data of 89 angiogenesis-related genes obtained by microarray hybridization from the database of the US National Cancer Institute with the 50% growth inhibition concentration values for eight ARSs (ARS, arteether (ARE), artesunate (ART), artemisetene, arteanuine B, dihydroartemisinylester stereoisomers 1 and 2). The constitutive expression of 30 genes correlated significantly with the cellular response to ARSs. By means of hierarchical cluster analysis and cluster image mapping expression, profiles were identified that determined significantly the cellular response to ART, ARE, artemether and dihydroartemisinylester stereoisomer 1. We have exemplarily validated the microarray data of six out of these 30 genes by realtime RT-PCR in seven cell lines. The fact that sensitivity and resistance of tumor cells could be predicted by the mRNA expression of angiogenesisrelated genes indicate that ARSs reveal their antitumor effects at least in part by inhibition of tumor angiogenesis. As many chemopreventive drugs exert antiangiogenic features, ARSs might also be chemopreventive in addition to their cytotoxic effects.

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Section: Discussionmentioning

confidence: 99%

Section: Cell Culturementioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Microarray expression profiles of angiogenesis-related genes predict tumor cell response to artemisinins

et al. 2006

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“…In 2001 Efferth et al reported that artesunate showed antitumor activity against 55 tumor cell lines, and it was most active against leukemia and colon cancer cell lines. It is notable that none of CEM leukemia sublines, resistant to doxorubicin, vincristin, methotrexate or hydroxyurea showed cross-resistance to artesunate [39] . Since then, more new artemisinin derivatives and analogs were synthesized and tested against human cancer cells.…”

mentioning

confidence: 99%

Qinghaosu (artemisinin): Chemistry and pharmacology

2012

Acta Pharmacol Sin

126

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Qinghaosu and its derivatives are widely used in the world as a new generation of antimalarial drug. Up to now, some important progresses of Qinghaosu research have been made, including synthesis of new Qinghaosu derivatives and analogs, investigation on their bioactivities and mode of actions. The present review briefly describes these efforts made by researchers in China, particularly in this Institute.Keywords: Qinghaosu; artemisinin; structure modification; antimalarial activity; anticancer activity; immunosuppressive activity; mode of action Acta Pharmacologica Sinica (2012) 33: 1141-1146; doi: 10.1038/aps.2012.104; published online 27 Aug 2012On 23rd May 1967, China established National Steering Group on antimalarial drug research, more than 60 institutes and 500 researchers joined in this project. After screening of over 5000 traditional Chinese medicines, Qinghaosu (QHS), an antimalarial principle, was isolated from Artemisia annua L in 1972 [1,2] . At the end of 1975, its unique chemical structure was elucidated, as a sesquiterpene lactone bearing a peroxy group, quite different from that of all known antimalarial drugs [3] .Early pharmacological and clinic studies showed QHS have rapid onset of action, low toxicity and high effect on both drug-resistant and drug-sensitive malaria. However, its shortcomings (poor solubility in water or oil; high rate of parasite recrudescence) needed to be overcome. In 1976, our Institute was charged with this important mission, and a research in relationship between chemical structure and activity immediately started.First of all, the function of peroxy group for antimalarial activity was examined. The negative result of deoxyqinghaosu (Scheme 1) against P berghei in mice demonstrated that the peroxy group was essential. Soon afterwards, it was found that some other simple peroxides including monoterpene ascaridol had no antimalarial activity. These experimental results proved peroxy group to be an essential but not a sufficient factor. At that time, we noted the molecule contained a rare segment -O-C-O-C-O-C=O, and realized that whole molecular skeleton might play an important role for antimalarial activity.When dihydroartemisinin (DHA) was found to be more active than QHS, but was still with poor solubility and lower stability (as a lactol) than QHS, we decided to prepare its derivatives. In 1976-1977, over 50 derivatives of DHA were synthesized (Scheme 1) and evaluated [4,5] .The first 25 compounds (in oil solution) were tested in mice infected chloroquine-resistant P berghei though intramuscular injection [6] . Most of these derivatives showed higher activity than QHS (SD 50 6.20 mg/kg) and DHA (SD 50 3.65 mg/kg). In the ether series, SM 224 (R=CH 3 , SD 50 1.02 mg/kg) is more

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Affordable and rapid HPTLC method for the simultaneous analysis of artemisinin and its metabolite artemisinic acid in Artemisia annua L.

Khan

Ali

Ahmad

et al. 2015

Biomedical Chromatography

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Artemisinin (AN) and artemisinic acid (AA), valuable phyto-pharmaceutical molecules, are well known anti-malarials, but their activities against diseases like cancer, schistosomiasis, HIV, hepatitis-B and leishmaniasis are also being reported. For the simultaneous estimation of AN and AA in the callus and leaf extracts of A. annua L. plants, we embarked upon a simple, rapid, selective, reliable and fairly economical high performance thin layer chromatography (HPTLC) method. Experimental conditions such as band size, chamber saturation time, migration of solvent front and slit width were critically studied and the optimum conditions were selected. The separations were achieved using toluene-ethyl acetate, 9:1 (v/v) as mobile phase on pre-coated silica gel plates, G 60F254 . Good resolution was achieved with Rf values of 0.35 ± 0.02 and 0.26 ± 0.02 at 536 nm for AN and 626 nm for AA, respectively, in absorption-reflectance mode. The method displayed a linear relationship with r(2) value 0.992 and 0.994 for AN and AA, respectively, in the concentration range of 300-1500 ng for AN and 200-1000 ng for AA. The method was validated for specificity by obtaining in-situ UV overlay spectra and sensitivity by estimating limit of detection (30 ng for AN and 15 ng for AA) and limit of quantitation (80 ng for AN and 45 ng for AA) values. The accuracy was checked by the recovery studies conducted at three different levels with the known concentrations and the average percentage recovery was 101.99% for AN and 103.84% for AA. The precision was analyzed by interday and intraday precision and was 1.09 and 1.00% RSD for AN and 1.22 and 6.05% RSD for AA. The analysis of statistical data substantiates that this HPTLC method can be used for the simultaneous estimation of AN and AA in biological samples.

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The anti-malarial artesunate is also active against cancer

Cited by 324 publications

References 0 publications

Microarray expression profiles of angiogenesis-related genes predict tumor cell response to artemisinins

Microarray expression profiles of angiogenesis-related genes predict tumor cell response to artemisinins

Qinghaosu (artemisinin): Chemistry and pharmacology

Affordable and rapid HPTLC method for the simultaneous analysis of artemisinin and its metabolite artemisinic acid in Artemisia annua L.

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