title: Dihydroartemisinin increases temozolomide efficacy in glioma cells by inducing autophagy.
abstract: Artemisinin, a powerful antimalarial medicine, is extracted from the Chinese herb,Artemisia annuaL., and has the ability to inhibit the proliferation of cancer cells. Dihydroartemisinin (DHA), the major active metabolite of artemisinin, is able to inhibit the growth of a variety of types of human cancer. However, the effect of DHA on human glioma cells remains unclear. The aim of the present study was to investigate the effect of DHA on the proliferation of glioma cells, and whether DHA was able to enhance temozolomide (TMZ) sensitivityin vitroandin vivo. In total, 10 human glioma cell lines were used to analyze the growth inhibition ability of DHA by MTT assay. The typical autophagic vacuoles were monitored by the application of the autofluorescent agent, monodansylcadaverine. Western blotting was used to detect markers of apoptosis and autophagy, namely Caspase-3, Beclin-1 and LC3-B. The combination efficiency of DHA and TMZ was assessedin vitroandin vivo. The half maximal inhibitory concentration (IC50) of DHA differed among the ten human glioma cell lines. The number of autophagic vacuoles was higher in DHA-treated SKMG-4 cells; this was highest of all cell lines analyzed. The expression of autophagy molecular markers, Beclin-1 and LC3-B, was increased following DHA treatment, while no significant alteration was detected in the expression of apoptotic marker Caspase-3. When combined with DHA, the IC50of TMZ decreased significantly in the four glioma cell lines analyzed. Furthermore, DHA enhanced the tumor inhibition ability of TMZ in tumor-burdened mice. The results of the present study demonstrated that DHA inhibited the proliferation of glioma cells and enhanced the tumor inhibition efficacy of TMZin vitroandin vivothrough the induction of autophagy.
authors.affiliation: Department of Neurosurgery, Guangdong Provincial Hospital of Traditional Chinese Medicine, Guangzhou, Guangdong 510120, P.R. China.
authors.forename: Ze-Shun
authors.initials: ZS
authors.lastname: Zhang
authors.affiliation: Department of Neurosurgery/Neuro-Oncology, Sun Yat-Sen University Cancer Center; State Key Laboratory of Oncology in South China; Collaborative Innovation Center for Cancer Medicine, Guangzhou, Guangdong 510060, P.R. China.
authors.forename: Jing
authors.initials: J
authors.lastname: Wang
authors.affiliation: Department of Neurosurgery, Guangdong Provincial Hospital of Traditional Chinese Medicine, Guangzhou, Guangdong 510120, P.R. China.
authors.forename: You-Bi
authors.initials: YB
authors.lastname: Shen
authors.affiliation: Department of Neurosurgery/Neuro-Oncology, Sun Yat-Sen University Cancer Center; State Key Laboratory of Oncology in South China; Collaborative Innovation Center for Cancer Medicine, Guangzhou, Guangdong 510060, P.R. China.
authors.forename: Cheng-Cheng
authors.initials: CC
authors.lastname: Guo
authors.affiliation: Department of Neurosurgery/Neuro-Oncology, Sun Yat-Sen University Cancer Center; State Key Laboratory of Oncology in South China; Collaborative Innovation Center for Cancer Medicine, Guangzhou, Guangdong 510060, P.R. China.
authors.forename: K E
authors.initials: KE
authors.lastname: Sai
authors.affiliation: Department of Neurosurgery/Neuro-Oncology, Sun Yat-Sen University Cancer Center; State Key Laboratory of Oncology in South China; Collaborative Innovation Center for Cancer Medicine, Guangzhou, Guangdong 510060, P.R. China.
authors.forename: Fu-Rong
authors.initials: FR
authors.lastname: Chen
authors.affiliation: Department of Neurosurgery/Neuro-Oncology, Sun Yat-Sen University Cancer Center; State Key Laboratory of Oncology in South China; Collaborative Innovation Center for Cancer Medicine, Guangzhou, Guangdong 510060, P.R. China.
authors.forename: Xin
authors.initials: X
authors.lastname: Mei
authors.affiliation: Department of Neurosurgery, Guangdong Provincial Hospital of Traditional Chinese Medicine, Guangzhou, Guangdong 510120, P.R. China.
authors.forename: F U
authors.initials: FU
authors.lastname: Han
authors.affiliation: Department of Neurosurgery/Neuro-Oncology, Sun Yat-Sen University Cancer Center; State Key Laboratory of Oncology in South China; Collaborative Innovation Center for Cancer Medicine, Guangzhou, Guangdong 510060, P.R. China.
authors.forename: Zhong-Ping
authors.initials: ZP
authors.lastname: Chen
keywords: autophagy; dihydroartemisinin; glioma; temozolomide