Skip to Content
Merck
  • Artesunate suppresses tumor growth and induces apoptosis through the modulation of multiple oncogenic cascades in a chronic myeloid leukemia xenograft mouse model.

Artesunate suppresses tumor growth and induces apoptosis through the modulation of multiple oncogenic cascades in a chronic myeloid leukemia xenograft mouse model.

Oncotarget (2015-03-05)
Chulwon Kim, Jong Hyun Lee, Sung-Hoon Kim, Gautam Sethi, Kwang Seok Ahn
ABSTRACT

Artesunate (ART), a semi-synthetic derivative of artemisinin, is one of the most commonly used anti-malarial drugs. Also, ART possesses anticancer potential albeit through incompletely understood molecular mechanism(s). Here, the effect of ART on various protein kinases, associated gene products, cellular response, and apoptosis was investigated. The in vivo effect of ART on the growth of human CML xenograft tumors in athymic nu/nu mice was also examined. In our preliminary experiments, we first observed that phosphorylation of p38, ERK, CREB, Chk-2, STAT5, and RSK proteins were suppressed upon ART exposure. Interestingly, ART induced the expression of SOCS-1 protein and depletion of SOCS-1 using siRNA abrogated the STAT5 inhibitory effect of the drug. Also various dephosphorylations caused by ART led to the suppression of various survival gene products and induced apoptosis through caspase-3 activation. Moreover, ART also substantially potentiated the apoptosis induced by chemotherapeutic agents. Finally, when administered intraperitoneally, ART inhibited p38, ERK, STAT5, and CREB activation in tumor tissues and the growth of human CML xenograft tumors in mice without exhibiting any significant adverse effects. Overall, our results suggest that ART exerts its anti-proliferative and pro-apoptotic effects through suppression of multiple signaling cascades in CML both in vitro and in vivo.

MATERIALS
Product Number
Brand
Product Description

Supelco
Glycine, analytical standard, for nitrogen determination according to Kjeldahl method
Sigma-Aldrich
Sodium dodecyl sulfate, ≥99.0% (GC), dust-free pellets
Sigma-Aldrich
Sodium dodecyl sulfate, ACS reagent, ≥99.0%
Sigma-Aldrich
Sodium chloride solution, 0.85%
Sigma-Aldrich
MISSION® esiRNA, targeting mouse Socs1
Supelco
Sodium dodecyl sulfate, dust-free pellets, suitable for electrophoresis, for molecular biology, ≥99.0% (GC)
SAFC
Sodium chloride solution, 5 M
Sigma-Aldrich
Sodium chloride, BioPerformance Certified, ≥99% (titration), suitable for insect cell culture, suitable for plant cell culture
Supelco
Glycine, certified reference material, TraceCERT®, Manufactured by: Sigma-Aldrich Production GmbH, Switzerland
Glycine, European Pharmacopoeia (EP) Reference Standard
USP
Glycine, United States Pharmacopeia (USP) Reference Standard
Sigma-Aldrich
Sodium dodecyl sulfate, BioUltra, for molecular biology, ≥99.0% (GC)
Sigma-Aldrich
Sodium dodecyl sulfate, ≥98.0% (GC)
Sigma-Aldrich
Sodium dodecyl sulfate, tested according to NF, mixture of sodium alkyl sulfates consisting mainly of sodium dodecyl sulfate
Supelco
Sodium dodecyl sulfate, suitable for ion pair chromatography, LiChropur, ≥99.0%
SAFC
Glycine
Sigma-Aldrich
Tris(hydroxymethyl)aminomethane, ACS reagent, ≥99.8%
Sigma-Aldrich
Glycine, ACS reagent, ≥98.5%
Sigma-Aldrich
Glycine, puriss. p.a., reag. Ph. Eur., buffer substance, 99.7-101% (calc. to the dried substance)
Sigma-Aldrich
Sodium chloride, 99.999% trace metals basis
Sigma-Aldrich
Sodium trichloroacetate, 97%
Sigma-Aldrich
Glycine, 99%, FCC
Supelco
Sodium chloride, reference material for titrimetry, certified by BAM, >99.5%
Sigma-Aldrich
Trizma® base, BioUltra, for molecular biology, ≥99.8% (T)
Supelco
Trizma® base, reference material for titrimetry, certified by BAM, >99.5%
Sigma-Aldrich
Glycine, BioUltra, for molecular biology, ≥99.0% (NT)
Sigma-Aldrich
Sodium dodecyl sulfate, ≥98.0% (GC)
Sigma-Aldrich
Sodium chloride, BioUltra, for molecular biology, ≥99.5% (AT)
Sigma-Aldrich
Glycine, tested according to Ph. Eur.
Sigma-Aldrich
Trizma® base, ≥99.0% (T)