Artesunate inhibits growth and induces apoptosis in human osteosarcoma HOS cell line in vitro and in vivo

Xu, Qiang; Li, Zhaoxu; Peng, Huiqin; Sun, Zhengwang; Cheng, Rui-lin; Ye, Zhaoming; Li, Weixu

doi:10.1631/jzus.b1000373

Cited by 49 publications

(30 citation statements)

References 34 publications

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“…Recently, Xu et al demonstrated that the antitumor mechanism of artesunate was achieved by inhibiting cell cycle progression and inducing apoptosis in human osteosarcoma cells in vitro and in vivo [26]. In this study, FCM was used to detect changes in cell cycle progression, and it was found that as the artesunate concentration increased, the proportion of MG-63 cells in the G2/M and S phases gradually increased while the proportion of cells at G0/G1 phase gradually decreased, which indicated that artesunate inhibited the progression of cell cycle thereby restraining cell proliferation.…”

Section: Discussionmentioning

confidence: 99%

Artesunate Decreases β-Catenin Expression, Cell Proliferation and Apoptosis Resistance in the MG-63 Human Osteosarcoma Cell Line

Chen

Gong

et al. 2017

Cell Physiol Biochem

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Background: This study aims to determine the effects of artesunate on proliferation, apoptosis and β-catenin expression in the human osteosarcoma cell line MG-63. Methods: MG-63 cells in the logarithmic growth phase were collected and cultured with different concentrations of artesunate (12.5 µg/mL, 25 µg/mL and 50 µg/mL) for 24 h, 48 h and 72 h. The total number of MG-63 cells and the morphological changes were observed under an inverted microscope. The MTT assay was adopted to test the inhibition rate (IR) of cell growth. The apoptosis rate was detected using annexin V/propidium iodide (PI) staining. Cell cycle distribution was identified by flow cytometry (FCM), and the expression levels of β-catenin, cyclins and cyclin dependent kinases (CDKs) were measured using Western blotting. Results: The results of the MTT assay indicated that artesunate could remarkably inhibit MG-63 cell proliferation compared with the rates in the untreated control group (0 µg/mL artesunate), and the inhibitory effect was dose-dependent. The apoptosis rate of MG-63 cells was elevated as the concentration of artesunate increased, and all the rates were significantly higher than that in the control group. Additionally, as the artesunate concentration increased, the proportion of MG-63 cells in G0/G1 phase gradually declined whereas that of cells in the G2/M and S phases increased. Western blotting confirmed that a higher concentration of artesunate reduced the expression levels of β-catenin, cyclin A, cyclin D1 and CDK1 and increased the expression levels of cyclin B1; however, artesunate had no impact on CDK2 expression in MG-63 cells. Conclusion: These results demonstrated that artesunate can inhibit β-catenin expression and cell proliferation as well as promote cell apoptosis in MG-63 cells, which indicates that artesunate may serve as a promising drug in the clinical treatment of osteosarcoma.

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Section: Discussionmentioning

confidence: 99%

Artesunate Decreases β-Catenin Expression, Cell Proliferation and Apoptosis Resistance in the MG-63 Human Osteosarcoma Cell Line

Chen

Gong

et al. 2017

Cell Physiol Biochem

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“…Interestingly, the effect on total metabolic activity was not reversed up to 96 hpt. The explanation for this apparent discrepancy is probably linked to a cell cycle arrest in G 0 or G 2 , as previously demonstrated in other cells (39,(54)(55)(56). When the effect of artesunate waned, a high proportion of the synchronized cells moved into the S phase and incorporated BrdU in their DNA, whereas the metabolic activity was still reduced due to reduced cell numbers.…”

Section: Discussionmentioning

confidence: 72%

Antiviral Effects of Artesunate on JC Polyomavirus Replication in COS-7 Cells

Sharma

Marschall

Rinaldo

2014

Antimicrob Agents Chemother

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The human JC polyomavirus (JCPyV) causes the fatal demyelinating disease progressive multifocal leukoencephalopathy (PML). A growing number of patients with induced or acquired immunosuppression are at risk for infection, and no effective antiviral therapy is presently available. The widely used antimalarial drug artesunate has shown broad antiviral activity in vitro but limited clinical success. The aim of this study was to investigate the effect of artesunate on JCPyV replication in vitro. The permissivity for JCPyV MAD-4 was first compared in four cell lines, and the monkey kidney cell line COS-7 was selected. Artesunate caused a concentration-dependent decrease in the extracellular JCPyV DNA load 96 h postinfection, with a 50% effective concentration (EC 50 ) of 2.9 M. This effect correlated with a decreased expression of capsid protein VP1 and a reduced release of infectious viral progeny. For concentrations of <20 M, transient reductions in cellular DNA replication and proliferation were seen, while for higher concentrations, some cytotoxicity was detected. A selective index of 16.6 was found when cytotoxicity was calculated based on cellular DNA replication in the mock-infected cells, but interestingly, cellular DNA replication in the JCPyV-infected cells was more strongly affected. In conclusion, artesunate is efficacious in inhibiting JCPyV replication at micromolar concentrations, which are achievable in plasma. The inhibition at EC 50 probably reflects an effect on cellular proteins and involves transient cytostatic effects. Our results, together with the favorable distribution of the active metabolite dihydroartemisinin to the central nervous system, suggest a potential use for artesunate in patients with PML.

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“…Interestingly, while some found simultaneously increased numbers of cells in G 0 /G 1 phase (43) (45), others described increased numbers of cells in G 2 /M phase (46). Apparently, artesunate also induced apoptosis in many cancer cell lines (43,45,46). Since we did not detect any sub-G 1 -phase fraction when performing flow cytometry, we concluded that artesunate at 10 and 40 M does not induce apoptosis in RPTECs.…”

Section: Discussionmentioning

confidence: 72%

“…This is also supported by our real-time proliferation analysis, where only cells treated with artesunate at concentrations of 10 M or less, which were possibly arrested in G 0 phase, spontaneously reinitiated proliferation after 40 to 50 h. Of note, artesunate and dihydroartemisinin have previously been described to decrease the numbers of cells in S phase in A431 human epidermoid carcinoma cells (43), cells of the human leukemia cell line K562 (44), and cells of the murine myeloma cell line SP2/0 (45). Interestingly, while some found simultaneously increased numbers of cells in G 0 /G 1 phase (43) (45), others described increased numbers of cells in G 2 /M phase (46). Apparently, artesunate also induced apoptosis in many cancer cell lines (43,45,46).…”

Section: Discussionmentioning

confidence: 99%

Antiviral Effects of Artesunate on Polyomavirus BK Replication in Primary Human Kidney Cells

Sharma

Marschall

Henriksen

et al. 2014

Antimicrob Agents Chemother

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dPolyomavirus BK (BKV) causes polyomavirus-associated nephropathy (PyVAN) and hemorrhagic cystitis (PyVHC) in renal and bone marrow transplant patients, respectively. Antiviral drugs with targeted activity against BKV are lacking. Since the antimalarial drug artesunate was recently demonstrated to have antiviral activity, the possible effects of artesunate on BKV replication in human primary renal proximal tubular epithelial cells (RPTECs), the host cells in PyVAN, were explored. At 2 h postinfection (hpi), RPTECs were treated with artesunate at concentrations ranging from 0.3 to 80 M. After one viral replication cycle (approximately 72 hpi), the loads of extracellular BKV DNA, reflecting viral progeny production, were reduced in a concentrationdependent manner. Artesunate at 10 M reduced the extracellular BKV load by 65%; early large T antigen mRNA and protein expression by 30% and 75%, respectively; DNA replication by 73%; and late VP1 mRNA and protein expression by 47% and 64%, respectively. Importantly, the proliferation of RPTECs was also inhibited in a concentration-dependent manner. At 72 hpi, artesunate at 10 M reduced cellular DNA replication by 68% and total metabolic activity by 47%. Cell impedance and lactate dehydrogenase measurements indicated a cytostatic but not a cytotoxic mechanism. Flow cytometry and 5-ethynyl-2=-deoxyuridine incorporation revealed a decreased number of cells in S phase and suggested cell cycle arrest in G 0 or G 2 phase. Both the antiproliferative and antiviral effects of artesunate at 10 M were reversible. Thus, artesunate inhibits BKV replication in RPTECs in a concentration-dependent manner by inhibiting BKV gene expression and genome replication. The antiviral mechanism appears to be closely connected to cytostatic effects on the host cell, underscoring the dependence of BKV on host cell proliferative functions.

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Artesunate inhibits growth and induces apoptosis in human osteosarcoma HOS cell line in vitro and in vivo

Cited by 49 publications

References 34 publications

Artesunate Decreases β-Catenin Expression, Cell Proliferation and Apoptosis Resistance in the MG-63 Human Osteosarcoma Cell Line

Artesunate Decreases β-Catenin Expression, Cell Proliferation and Apoptosis Resistance in the MG-63 Human Osteosarcoma Cell Line

Antiviral Effects of Artesunate on JC Polyomavirus Replication in COS-7 Cells

Antiviral Effects of Artesunate on Polyomavirus BK Replication in Primary Human Kidney Cells

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