Artesunate inhibits angiogenesis and downregulates vascular endothelial growth factor expression in chronic myeloid leukemi

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Vascul Pharmacol. 2007 Aug-Sep;47(2-3):131-8. Epub 2007 May 24.

Artesunate
inhibits angiogenesis and downregulates vascular endothelial growth
factor expression in chronic myeloid leukemia K562 cells.

 
Zhou HJ, Wang WQ, Wu GD, Lee J, Li A.
Institute
of Pharmacology and Toxicology, School of Pharmaceutical Sciences,
Zhejiang University, Hangzhou 310031, PR China.

Artesunate
(ART), a semi-synthetic derivative of artemisinin extracted from the
Chinese herb Artemisia annua, is a safe and effective antimalarial
drug. In the present investigation, we analyzed the inhibitory effects
of ART on angiogenesis and on VEGF production in chronic myeloid
leukemia (CML) K562 cells in vitro and in vivo. In order to analyze the
effect of ART on VEGF secretion in K562 cells, we examined the level of
VEGF secreted in conditioned media (CM) by ELISA assay. The result
showed that ART could decrease the VEGF level in CM of K562 cells, even
at a lower concentration (2 micromol/l, P<0.01). The inhibitory
effect of in vitro angiogenesis was tested on aortic sprouting in
fibrin gel. ART could effectively suppress the stimulating angiogenic
ability of CM by pretreated with K562 cells for 48 h in a
time-dependent manner (days 3-14). The antiangiogenic effect of ART was
further evaluated in vivo in chicken chorioallantoic membrane (CAM)
neovascularization model. The result indicated that the stimulating
angiogenic activity was decreased in response to the K562 cells treated
with ART or the CM from K562 cells pretreated with ART in a
dose-dependent manner (3-12 micromol/l). Furthermore, we analyzed the
level of VEGF expression by western blot and detected the form of VEGF
mRNA by RT-PCR in K562 cells. The experiments showed that ART could
inhibit the VEGF expression, correlated well with the level of VEGF
secreted in CM. These findings suggest that ART might present potential
antileukemia effect as a treatment for CML therapy, or as an adjunct to
standard chemotherapeutic regimens.