Dihydroartemisinin inhibits the Raf/ERK/MEK and PI3K/AKT pathways in glioma cells

Du, Wei; Pang, Chun; Xue, Yue; Zhang, Qingjun; Wei, Xinting

doi:10.3892/ol.2015.3699

Cited by 30 publications

(20 citation statements)

References 25 publications

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“…We further investigated the potential downstream pathways that might be responsible for the repressive effect of anti-miR-21 + sh-CXCR4 on tumor progression. In this study, we focused on two pathways 1) PI3K/AKT and 2) Raf/ MEK/ ERK, which both played a vital role in glioma cell fate, and were aberrant in the miR-21 and/or CXCR4 overexpression environment (Ching and Hansel 2010, Guo et al, 2013, Dongfeng et al, 2014, Du et al, 2015, Han et al, 2016, Shao et al 2017). The results from western blot analysis presented no statistically difference in AKT, ERK1/2 among different treatment groups both in glioma cells and xenografts (Fig.…”

Section: Resultsmentioning

confidence: 99%

Double-targeted knockdown of miR-21 and CXCR4 inhibits malignant glioma progression by suppression of the PI3K/AKT and Raf/MEK/ERK pathways

Liu

Yang

2020

Preprint

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Background: Currently, miR-21 and CXCR4 are being extensively investigated as two unrelated key regulators in glioma malignancy. In this study, we investigated the combined effect of these two factors on glioma progression. Methods:We confirmed the expression of miR-21 and CXCR4 in malignant glioma tissue and glioma cells with qRT-PCR and western blotting. Single-targeted knockdown of miR-21 and CXCR4, as well as double-targeted knockdown of miR-21 and CXCR4 lentiviral vectors were constructed and they were transfected to U87 and U251 cells. Cell proliferation, apoptosis, invasion, and migration from different treatment groups were assessed by MTT assay, Flow Cytometry analysis, Transwell analysis, and Scratch assay, respectively. U87 xenograft mice were constructed to detect roles and potential mechanisms of miR-21 and CXCR4 in malignant glioma tumor growth. Results:The expression of miR-21 and CXCR4 was increased in tumor tissues and cell lines. Inhibition of miR-21, CXCR4, and miR-21 and CXCR4 together all reduced the migration, invasiveness, proliferation and enhanced apoptosis in glioma cells, as well as reduced tumor volume and mass in xenograft model. The inhibition effect was strongest in double-targeted knockdown of miR-21 and CXCR4 group, whose downstream pathways involved in AKT axis and ERK axis activation. Conclusions:Our findings reported that double-targeted knockdown of miR-21 and CXCR4 could more effectively inhibit the proliferation, migration, invasion and growth of transplanted tumor and promote cell apoptosis, which were involved in the PI3K/AKT and Raf/MEK/ERK signaling pathways.

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Section: Resultsmentioning

confidence: 99%

Double-targeted knockdown of miR-21 and CXCR4 inhibits malignant glioma progression by suppression of the PI3K/AKT and Raf/MEK/ERK pathways

Liu

Yang

2020

Preprint

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“…DHA is an effective drug in treating patients with malaria (22). Recent studies have revealed that DHA has antitumor activity with few side effects in various types of tumors in vivo and in vitro (16)(17)(18)(23)(24)(25). Based on the results of these aforementioned studies, the present study investigated the therapeutic role of DHA and its underlying mechanism in T-cell lymphoma cells.…”

Section: Discussionmentioning

confidence: 96%

“…The Akt/GSK3β signaling pathway is activated upon phosphorylation of Akt and GSK3β at serine 473 and serine 9, respectively, and promotes proliferation and inhibits apoptosis. Previous studies have demonstrated that DHA could inhibit the Akt/GSK3β signaling pathway in lung cancer and glioma cells (23,25). To further elucidate the mechanism of DHA treatment in T-cell lymphoma cells, the present study investigated the effect of DHA on the Akt/GSK3β signaling pathway.…”

Section: Discussionmentioning

confidence: 97%

Dihydroartemisinin triggers c‑Myc proteolysis and inhibits protein kinase B/glycogen synthase kinase 3β pathway in T‑cell lymphoma cells

Wei

Zhao

et al. 2018

Oncol Lett

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Recent studies have revealed a positive therapeutic effect of dihydroartemisinin (DHA) on tumor cells. However, the underlying mechanism of this has not yet been elucidated. The present study examined the potential therapeutic role and mechanism of DHA in T-cell lymphoma cells. It was revealed that DHA inhibited the proliferation of Jurkat and HuT-78 T-cell lymphoma cells in a concentration-and time-dependent manner. Furthermore, DHA reduced c-Myc protein expression at the transcriptional level, and induced the phosphorylation of c-Myc and the degradation of c-Myc oncoprotein levels. DHA treatment resulted in decreased phosphorylation of protein kinase B (Akt) and glycogen synthase 3β (GSK3β) in T-cell lymphoma cells. In addition, DHA treatment induced cell apoptosis, which was accompanied by an increased ratio of Bax/Bcl-2. Taken together, the results of the present study suggested that DHA may exert its antitumor role by accelerating c-Myc proteolysis and inhibiting the Akt/GSK3β pathway in T-cell lymphoma cells.

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“…As an anti‐apoptotic protein, HSP70 is highly expressed in breast, liver and prostate cancer (Kita et al, ; Ren et al, ; Yue et al, ). Silencing the expression of HSP70 can induce the apoptosis of human prostate cancer PC‐3M cells, as the protein inhibits the apoptosis of prostate cancer cells (Du, Pang, Xue, Zhang, & Wei, ). Therefore, following treatment of PC‐3 cells with DHA, the expression levels of HSP70 mRNA and protein were downregulated ( p < 0.05).…”

Section: Discussionmentioning

confidence: 99%

Effects of dihydroartemisinin on HSP70 expression in human prostate cancer PC‐3 cells

Kong

et al. 2019

Andrologia

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We aimed to evaluate the effects of dihydroartemisinin (DHA) on heat‐shock protein 70 (HSP70) expression in human prostate cancer PC‐3 cells and to examine the molecular mechanism. The viability of PC‐3 cells following treatment with 25, 50, 100 and 200 μmol/L DHA for 48 hr was detected by flow cytometry and MTT assay. The expression of HSP70 mRNA was detected by RT‐qPCR. The expression levels and locations of HSP70, caspase‐3 and apoptosis‐inducing factor (AIF) were detected with immunofluorescence assay. With 100 μmol/L HSP70 inhibitor quercetin as positive control and dimethyl sulphoxide (DMSO) as solvent control, the protein expressions of HSP70, apoptotic protease activating factor‐1 (Apaf‐1) and AIF were detected by Western blot. DHA promoted PC‐3 cell apoptosis dose‐dependently. With increasing DHA dose, the expression of HSP70 mRNA significantly decreased (p < 0.05). DHA did not change the location of HSP70 or AIF. Compared with control and DMSO groups, the expression of HSP70 protein significantly decreased, and those of Apaf‐1, caspase‐3 and AIF significantly increased following treatment with DHA and quercetin for 48 hr. In conclusion, DHA inhibits the expression of HSP70 and induces the apoptosis of PC‐3 cells. The results provide valuable experimental evidence for prostate cancer therapies using DHA.

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Dihydroartemisinin inhibits the Raf/ERK/MEK and PI3K/AKT pathways in glioma cells

Cited by 30 publications

References 25 publications

Double-targeted knockdown of miR-21 and CXCR4 inhibits malignant glioma progression by suppression of the PI3K/AKT and Raf/MEK/ERK pathways

Double-targeted knockdown of miR-21 and CXCR4 inhibits malignant glioma progression by suppression of the PI3K/AKT and Raf/MEK/ERK pathways

Dihydroartemisinin triggers c‑Myc proteolysis and inhibits protein kinase B/glycogen synthase kinase 3β pathway in T‑cell lymphoma cells

Effects of dihydroartemisinin on HSP70 expression in human prostate cancer PC‐3 cells

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