DHA regulates angiogenesis and improves the efficiency of CDDP for the treatment of lung carcinoma

Zhang, Jiali; Zeng, Wang; Hu, Wei; Chen, Sang-Sang; Lou, Xiang Yang; Zhou, Huijun

doi:10.1016/j.mvr.2013.02.006

Cited by 27 publications

(17 citation statements)

References 34 publications

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“…Previous studies have demonstrated the antiangiogenetic effects of DHA and other artemisinin derivatives (20,21). DHA has been shown to inhibit HUVEC migration in a dose-dependent manner (14), and also to reduce the migration of murine lymphatic ECs (22).…”

Section: Discussionmentioning

confidence: 98%

Dihydroartemisinin inhibits vascular endothelial growth factor-induced endothelial cell migration by a p38 mitogen-activated protein kinase-independent pathway

Guo¹,

Fang²,

Hou³

et al. 2014

Experimental and Therapeutic Medicine

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Dihydroartemisinin (DHA), a semi-synthetic derivative of artemisinin, has been demonstrated to possess a strong antiangiogenic activity. However, the molecular mechanisms underlying this effect remain unclear. Endothelial cell (EC) migration is an essential component of angiogenesis, and the p38 mitogen-activated protein kinase (MAPK) signaling pathway plays a key role in the regulation of migration induced by vascular endothelial growth factor (VEGF). The aim of the present study was to investigate the effects of DHA on EC migration and the p38 MAPK signaling pathway. Human umbilical vein ECs (HUVECs) were treated with DHA and VEGF-induced migration was analyzed. The activation of p38 MAPK was detected by western blot analysis, and the migration assays were performed with a p38-specific inhibitor, SB203850. It was revealed that 20 μM DHA significantly reduced EC migration in the transwell migration assay, wound healing assay and electrical cell-substrate impedance sensing real-time analysis. However, DHA did not affect p38 MAPK phosphorylation or expression. In the absence or presence of SB203850, DHA induced a similar proportional reduction of EC migration in the three migration assays. Therefore, the present study demonstrated that DHA inhibits VEGF-induced EC migration via a p38 MAPK-independent pathway.

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Section: Discussionmentioning

confidence: 98%

Dihydroartemisinin inhibits vascular endothelial growth factor-induced endothelial cell migration by a p38 mitogen-activated protein kinase-independent pathway

Guo¹,

Fang²,

Hou³

et al. 2014

Experimental and Therapeutic Medicine

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“…On the one hand, DHA treatment reduced hypoxia-induced HIF-1α activation and VEGF expression in multiple myeloma and C6 rat glioma cells resulting in reduced tumor cell growth and angiogenesis, respectively (23, 24). On the other hand, DHA enhanced the toxicity of cisplatinum in lung adenocarcinoma cells in vivo and this effect was accompanied by reduced expression of HIF-1α and VEGF and reduced tumor microvessel density (25). Interestingly, this anti-angiogenic effect of DHA was attributed to growth inhibition of endothelial cells and depended on the level of tissue oxygenation and the drug concentration (26).…”

Section: Discussionmentioning

confidence: 99%

“…Moreover, although not yet examined in clinical trials, DHA is able to improve treatment efficacy in combination with ionizing radiation or cisplatin in preclinical models (25, 28, 29) and thus shows great potential as anti-neoplastic drug.…”

Section: Discussionmentioning

confidence: 99%

Dihydroartemisinin is a Hypoxia-Active Anti-Cancer Drug in Colorectal Carcinoma Cells

et al. 2014

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Tumor hypoxia is one main biological factor that drives resistance to chemotherapy and radiotherapy. To develop a novel strategy for overcoming hypoxia-induced therapy resistance, we examined the anti-neoplastic activity of the reactive oxygen donor dihydroartemisinin (DHA) in human colon cancer cell lines in normoxia and severe hypoxia. In addition, we analyzed the involvement of the intrinsic apoptosis pathway for DHA-mediated cytotoxicity in HCT116 cells in short-term and long-term in vitro assays. When applied at lower concentrations (≤25 μM), DHA induced apoptosis in Colo205, HCT15, and HCT116 cells, whereas necrotic cell death was increased when cells were treated with higher DHA concentrations (50 μM). However, no preference for DHA-induced apoptosis or necrosis could be detected between the treatment under normoxic or hypoxic conditions. Moreover, DHA potently reduced clonogenic survival of HCT116 cells in normoxia and hypoxia. Treatment of HCT116 cells with 25 μM DHA resulted in activation of Bax under normoxic and hypoxic conditions. Interestingly, cytochrome c release from the mitochondria and caspase-activation were observed only under normoxic conditions, whereas, under hypoxic conditions DHA induced a caspase-independent apoptosis-like cell death. However, under both conditions, generation of reactive oxygen species was an important mediator of DHA-induced toxicity. Further molecular analysis suggests that DHA-mediated cell death involves different sets of pro-apoptotic Bcl-2 family members. The pronounced cytotoxic activity of DHA in severe hypoxia as well as normoxia offers new perspectives for targeting the hypoxic tumor cell fraction to improve treatment outcome for cancer patients.

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“…As CSCs have been recognized to be a crucial factor underlying the chemotherapy resistance of cancer tissues, the chemoresistance of the sorted SP cells against CDDP was also investigated. CDDP is a chemotherapeutic agent used in oncotherapy, which causes DNA crosslinking and ultimately induces apoptosis ( 57 ). The cellular viability of the SP and non-SP cells was decreased as the concentration of CDDP was increased.…”

Section: Discussionmentioning

confidence: 99%

Isolation and characterization of side population cells from the human ovarian cancer cell line SK-OV-3

Ruan

Liu

Kuang

2015

Experimental and Therapeutic Medicine

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Ovarian cancer (OC) is the most malignant type of gynecological tumor due to its high recurrence rate following initial treatment. Previous studies have indicated that cancer stem cells (CSCs) may be a potential cause underlying the high proportion of recurrence. Side population (SP) cells isolated from cancer cell lines have been shown to exhibit characteristics associated with CSCs, but studies on SP cells in human ovarian SK-OV-3 cell line are limited. In the present study, the SP cell fraction (4.83% of the total cell population) was isolated using flow cytometry, and analyzed by immunocytochemical analysis and reverse transcription-quantitative polymerase chain reaction. The results showed that SP cells exhibited a high mean fluorescence intensity for CD44, a CSC marker, in addition to elevated expression of the CSCs-associated genes, ATP-binding cassette sub-family G member 2 and Nestin. These findings indicated the stem cell-like features of the SP cells. Furthermore, a colony formation test showed that the isolated SP cells possessed a marked capacity for self-regeneration and proliferation. In addition, a cell cycle assay involving cisplatin indicated that the SP cells were strongly resistant to chemotherapy. In conclusion, the present results suggested that SP cells isolated from the SK-OV-3 cell line exhibited properties typically associated with CSCs. Therefore, the isolated SP cells may be used to provide novel insight into potential therapies against OC.

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DHA regulates angiogenesis and improves the efficiency of CDDP for the treatment of lung carcinoma

Cited by 27 publications

References 34 publications

Dihydroartemisinin inhibits vascular endothelial growth factor-induced endothelial cell migration by a p38 mitogen-activated protein kinase-independent pathway

Dihydroartemisinin inhibits vascular endothelial growth factor-induced endothelial cell migration by a p38 mitogen-activated protein kinase-independent pathway

Dihydroartemisinin is a Hypoxia-Active Anti-Cancer Drug in Colorectal Carcinoma Cells

Isolation and characterization of side population cells from the human ovarian cancer cell line SK-OV-3

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