Skip to Content
MilliporeSigma
  • 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

SAFC
Sodium chloride solution, 5 M
Supelco
Sodium dodecyl sulfate, dust-free pellets, suitable for electrophoresis, for molecular biology, ≥99.0% (GC)
Sigma-Aldrich
MISSION® esiRNA, targeting mouse Socs1
Glycine, European Pharmacopoeia (EP) Reference Standard
Trometamol, European Pharmacopoeia (EP) Reference Standard
USP
Tromethamine, United States Pharmacopeia (USP) Reference Standard
Supelco
Glycine, Pharmaceutical Secondary Standard; Certified Reference Material
Sigma-Aldrich
Tris(hydroxymethyl)aminomethane, ≥99.8%
Sigma-Aldrich
Tris(hydroxymethyl)aminomethane, JIS special grade, ≥99.0%
Sigma-Aldrich
Glycine, SAJ special grade, ≥99.0%
Sigma-Aldrich
Sodium dodecyl sulfate, ≥99.0%
Sigma-Aldrich
Sodium dodecyl sulfate, SAJ special grade, ≥97.0%
Sigma-Aldrich
Sodium chloride, JIS special grade, ≥99.5%
Sigma-Aldrich
Sodium dodecyl sulfate, ≥99.0% (GC), dust-free pellets
Sigma-Aldrich
Tris(hydroxymethyl)aminomethane, ≥99.8%
Sigma-Aldrich
Sodium chloride, SAJ first grade, ≥99.0%
Sigma-Aldrich
Sodium dodecyl sulfate, 92.5-100.5% based on total alkyl sulfate content basis
Sigma-Aldrich
Tromethamine, meets USP testing specifications
SAFC
Glycine
Sigma-Aldrich
Glycine, suitable for electrophoresis, ≥99%
Sigma-Aldrich
Sodium dodecyl sulfate, tested according to NF, mixture of sodium alkyl sulfates consisting mainly of sodium dodecyl sulfate
Sigma-Aldrich
Sodium chloride, BioUltra, for molecular biology, ≥99.5% (AT)
Sigma-Aldrich
Sodium dodecyl sulfate, BioUltra, for molecular biology, ≥99.0% (GC)
Sigma-Aldrich
Trizma® base, BioUltra, for molecular biology, ≥99.8% (T)
Sigma-Aldrich
Propidium iodide, ≥94.0% (HPLC)
Sigma-Aldrich
Glycine, ACS reagent, ≥98.5%
Sigma-Aldrich
Propidium iodide, ≥94% (HPLC)
Sigma-Aldrich
Sodium chloride, random crystals, optical grade, 99.9% trace metals basis
Sigma-Aldrich
Sodium chloride-35Cl, 99 atom % 35Cl
Sigma-Aldrich
Trizma® base, BioXtra, pH 10.5-12.0 (1 M in H2O), ≥99.9% (titration)