Dihydroartemisinin treatment of multiple myeloma cells causes activation of c-Jun leading to cell apoptosis

Wang,Yong; Xu,Xiaoyuan; Wu,Xiaojian; Chen,Weibin; Huang,Fangmei; Gui,Xiaomin

doi:10.3892/ol.2017.7582

Dihydroartemisinin treatment of multiple myeloma cells causes activation of c-Jun leading to cell apoptosis

Authors:
- Yong Wang
- Xiaoyuan Xu
- Xiaojian Wu
- Weibin Chen
- Fangmei Huang
- Xiaomin Gui
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Affiliations: Department of Hematology, The Affiliated Hospital of Jiujiang University College of Medicine, Jiujiang, Jiangxi 332000, P.R. China, Key Laboratory of System Bio‑Medicine of Jiangxi, Jiujiang University, Jiujiang, Jiangxi 332000, P.R. China
Published online on: December 11, 2017 https://doi.org/10.3892/ol.2017.7582
Pages: 2562-2566

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Abstract

The aim of the present study was to investigate the effect of dihydroartemisinin (DHA) on a multiple myeloma cell line. An MTT assay, flow cytometry and reverse transcription‑polymerase chain reaction (RT‑PCR) were used for the analysis of cell viability, cell cycle distribution and c‑Jun N‑terminal kinase (JNK) expression, respectively. Treatment of U266 cells using DHA caused a significant (P<0.05) decrease in cell viability compared with the control cells. An increase in the concentration of DHA from 1 to 100 µmol/l reduced cell viability from 87 to 35% compared with 100% in the control cultures at 48 h. A significant (P<0.05) increase was observed in the sub‑G0/G1 phase population of the U266 cells with an increase in DHA concentration from 1 to 100 µmol/l. Treatment with 1, 3, 10, 30 and 100 µmol/l concentrations of DHA increased the sub‑G0/G1 phase cell population to 3.13, 8.25, 24.91, 31.47 and 38.54%, respectively. RT‑PCR analysis of DHA‑treated or ‑untreated U266 cells after 48 h demonstrated a significant (P<0.01) increase in caspase‑3 expression. Treatment of the cells for 48 h with DHA led to a significant increase in c‑Jun expression. DHA treatment at 1, 3, 10, 30 and 100 µmol/l concentrations caused an increase in the level of c‑Jun by 0.174±0.001, 0.254±0.002, 0.387±0.001, 0.502±0.003 and 0.679±0.005, respectively, compared with 0.982±0.001 in the control cells. The addition of SP600125 to the cells incubated with DHA resulted in a significant decrease in the caspase‑3 and c‑Jun expression levels compared with those cells incubated with DHA alone. These findings confirm that treatment with DHA increased caspase‑3 and c‑Jun expression in the U266 cells through activation of the JNK signaling pathway. Thus, DHA inhibited proliferation of multiple myeloma cells by interfering with the JNK signaling pathway.

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