Please use this identifier to cite or link to this item: https://doi.org/10.18632/oncotarget.3004
Title: Artesunate suppresses tumor growth and induces apoptosis through the modulation of multiple oncogenic cascades in a chronic myeloid leukemia xenograft mouse model
Authors: Kim, C
Lee, J.H
Kim, S.-H
Sethi, G 
Ahn, K.S
Keywords: antimalarial agent
antineoplastic agent
artemisinin derivative
artesunate
animal
apoptosis
cell growth
drug effects
drug screening
female
genetics
human
Leukemia, Myelogenous, Chronic, BCR-ABL Positive
MCF-7 cell line
mouse
nude mouse
pathology
randomization
tumor cell line
Animals
Antimalarials
Antineoplastic Agents
Apoptosis
Artemisinins
Cell Growth Processes
Cell Line, Tumor
Female
Humans
Leukemia, Myelogenous, Chronic, BCR-ABL Positive
MCF-7 Cells
Mice
Mice, Nude
Random Allocation
Xenograft Model Antitumor Assays
Issue Date: 2015
Citation: Kim, C, Lee, J.H, Kim, S.-H, Sethi, G, Ahn, K.S (2015). Artesunate suppresses tumor growth and induces apoptosis through the modulation of multiple oncogenic cascades in a chronic myeloid leukemia xenograft mouse model. Oncotarget 6 (6) : 4020-4035. ScholarBank@NUS Repository. https://doi.org/10.18632/oncotarget.3004
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.
Source Title: Oncotarget
URI: https://scholarbank.nus.edu.sg/handle/10635/174128
ISSN: 19492553
DOI: 10.18632/oncotarget.3004
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