Dihydroartemisinin induces autophagy and inhibits the growth of iron‐loaded human myeloid leukemia K562 cells via ROS toxicity

Zeng, Wang; Hu, Wei; Zhang, Jiali; Wu, Xi; Zhou, Huijun

doi:10.1016/j.fob.2012.05.002

Cited by 80 publications

(42 citation statements)

References 38 publications

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“…Indeed, one recent report showed that ART induces autophagy via up-regulation of Beclin 1 expression (16). Moreover, our findings are consistent with three other reports suggesting that DHA was able to induce autophagy in cancer cells (57)(58)(59). DHA is a derivative of artemisinin, with a mechanistic action similar to that of ART (50,60).…”

Section: Discussionsupporting

confidence: 93%

Artesunate Induces Cell Death in Human Cancer Cells via Enhancing Lysosomal Function and Lysosomal Degradation of Ferritin

Yang

Tan

et al. 2014

Journal of Biological Chemistry

141

110

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Background: Artesunate is capable of inducing cell death in cancer cells. Results: Artesunate accumulates in lysosomes and promotes lysosomal function and ferritin degradation, leading to mitochondrial reactive oxygen species production and eventually cell death. Conclusion: Intracellular iron and ferritin degradation is essential for artesunate-induced lysosomal activation and cell death. Significance: This work reveals a novel mechanism underlying artesunate-induced cell death.

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Section: Discussionsupporting

confidence: 93%

Artesunate Induces Cell Death in Human Cancer Cells via Enhancing Lysosomal Function and Lysosomal Degradation of Ferritin

Yang

Tan

et al. 2014

Journal of Biological Chemistry

141

110

View full text Add to dashboard Cite

show abstract

“…It has been established that cancer cells produce higher levels of ROS than those of normal cells, as a result of metabolic stress and proliferative requirements. A previous study reported that DHA induced autophagy in the mitochondria of leukemia K562 cells (31). A further study found that the sensitivity of cancer cells to artemisinin was attenuated following the overexpression of oxidative stress associated enzymes (32).…”

Section: Discussionmentioning

confidence: 92%

Dihydroartemisinin increases temozolomide efficacy in glioma cells by inducing autophagy

et al. 2015

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Abstract. Artemisinin, a powerful antimalarial medicine, is extracted from the Chinese herb, Artemisia annua L., 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) sensitivity in vitro and in 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 assessed in vitro and in vivo. The half maximal inhibitory concentration (IC 50 ) 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 IC 50 of 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 TMZ in vitro and in vivo through the induction of autophagy.

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“…The results of the present study suggest that treatment with dihydroartemisinin significantly suppressed PARP levels in HCT116 cell. Wang et al (19) reported that dihydroartemisinin inhibits the growth and induces autophagy of iron-loaded human myeloid leukemia via PARP expression. These results suggest that transactivated PARP, caspase-3/9 and BAX each serve a role in dihydroartemisinin-induced apoptosis in CRC cells.…”

Section: Discussionmentioning

confidence: 99%

Dihydroartemisinin increases apoptosis of colon cancer cells through targeting Janus kinase 2/signal transducer and activator of transcription 3 signaling

et al. 2017

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Abstract. As a derivative of artemisinin, dihydroartemisinin is effective in the treatment of malaria. Dihydroartemisinin has been identified to possess inhibitory effects in numerous types of animal model with tumors, indicating that it has an antineoplastic effect. The aim of the present study was to analyze the potential anticancer effects of dihydroartemisinin, particularly its effect on apoptosis of colon cancer cells. In the present study, it was identified that dihydroartemisinin inhibited cell viability, promoted cell apoptosis, increased B-cell lymphoma-2-associated X-protein expression, increased caspase-3/9 activities, decreased poly(ADP-ribose) polymerase levels, decreased phosphorylation of extracellular-signal-regulated kinase, and increased phosphorylation of c-Jun N-terminal kinase and p38 mitogen-activated protein kinase in colon cancer cells. Conversely, the phosphorylation of Janus kinase 2 (JAK2) and signal transducer and activator of transcription 3 (STAT3) was suppressed by dihydroartemisinin in colon cancer cells. These results demonstrate that the potential anticancer effects of dihydroartemisinin may increase apoptosis of colon cancer cells through targeting JAK2/STAT3 signaling.

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Dihydroartemisinin induces autophagy and inhibits the growth of iron‐loaded human myeloid leukemia K562 cells via ROS toxicity

Abstract: Highlights► DHA induced K562 cells autophagy followed by LC3-II protein expression. ► The DHA-induced autophagy might be ROS dependent. ► Inhibition of K562 cell proliferation by DHA was also dependent upon iron decrease.

Cited by 80 publications

References 38 publications

Artesunate Induces Cell Death in Human Cancer Cells via Enhancing Lysosomal Function and Lysosomal Degradation of Ferritin

Artesunate Induces Cell Death in Human Cancer Cells via Enhancing Lysosomal Function and Lysosomal Degradation of Ferritin

Dihydroartemisinin increases temozolomide efficacy in glioma cells by inducing autophagy

Dihydroartemisinin increases apoptosis of colon cancer cells through targeting Janus kinase 2/signal transducer and activator of transcription 3 signaling

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