Dihydroartemisinin Enhances Apo2L/TRAIL-Mediated Apoptosis in Pancreatic Cancer Cells via ROS-Mediated Up-Regulation of Death Receptor 5

Kong, Rui; Chen, Zhangjian; Cheng, Zhuoxin; Wang, Yongwei; Mu, Ming; Wang, Shuangjia; Pan, Shangha; Gao, Yue; Jiang, Hongchi; Dong, De-Li; Sun, Bei

doi:10.1371/journal.pone.0037222

Cited by 61 publications

(44 citation statements)

References 52 publications

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“…DHA also substantially reduced tumor development in nude mice xenografted with BxPC-3 (Kong et al, 2012). Concordant with similar approach, another study highlighted ROS/ERK/p53-mediated upregulation of death receptors in Gamma-tocotrienol treated Panc-1 and MiaPaca-2 cells (Kannappan et al, 2010).…”

Section: Molecular Basis Of Trail Resistancesupporting

confidence: 58%

TRAIL Mediated Signaling in Pancreatic Cancer

Nogueira

Yaylım²,

Aamir³

et al. 2014

Asian Pacific Journal of Cancer Prevention

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Research over the years has progressively shown substantial broadening of the tumor necrosis factor alpharelated apoptosis-inducing ligand (TRAIL)-mediated signaling landscape. Increasingly it is being realized that pancreatic cancer is a multifaceted and genomically complex disease. Suppression of tumor suppressors, overexpression of oncogenes, epigenetic silencing, and loss of apoptosis are some of the extensively studied underlying mechanisms. Rapidly accumulating in vitro and in vivo evidence has started to shed light on the resistance mechanisms in pancreatic cancer cells. More interestingly a recent research has opened new horizons of miRNA regulation by DR5 in pancreatic cancer cells. It has been shown that DR5 interacts with the core microprocessor components Drosha and DGCR8, thus impairing processing of primary let-7. Xenografting DR5 silenced pancreatic cancer cells in SCID-mice indicated that there was notable suppression of tumor growth. There is a paradigm shift in our current understanding of TRAIL mediated signaling in pancreatic cancer cells that is now adding new layers of concepts into the existing scientific evidence. In this review we have attempted to provide an overview of recent advances in TRAIL mediated signaling in pancreatic cancer as evidenced byfindings of in vitro and in vivo analyses. Furthermore, we discuss nanotechnological advances with emphasis on PEG-TRAIL and four-arm PEG cross-linked hyaluronic acid (HA) hydrogels to improve availability of TRAIL at target sites.

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Section: Molecular Basis Of Trail Resistancesupporting

confidence: 58%

TRAIL Mediated Signaling in Pancreatic Cancer

Nogueira

Yaylım²,

Aamir³

et al. 2014

Asian Pacific Journal of Cancer Prevention

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“…Apoptosis induced by DHA in different cancer cells has been reported [21][22][23][24][25][26][27][28][29][30]. In the present study, we examined apoptosis in human androgen-independent PC3 prostate cancer cells after DHA treatment, by flow cytometry and TEM.…”

Section: Discussionmentioning

confidence: 82%

“…Dihydroartemisinin (DHA), a semisynthetic derivative of artemisinin isolated from the Chinese medicinal plant Artemisia annua L., has been widely used as an effective antimalarial drug [15][16][17][18][19]. Recently, many studies have shown that DHA is the most potent anticancer agent among artemisinin and its derivatives [20], and has in vitro and in vivo anticancer activity in different types of human cancer cells, such as hepatocellular carcinoma, prostate cancer, gastric cancer, osteosarcoma, breast cancer, esophageal cancer, pancreatic cancer, lung cancer, and ovarian cancer [21][22][23][24][25][26][27][28][29][30][31]. It has been demonstrated that DHA can induce apoptosis and/or inhibit proliferation of cancer cells [21][22][23][24][25][26][27][28][29][30][31].…”

Section: Introductionmentioning

confidence: 99%

Mechanism of dihydroartemisinin-induced apoptosis in prostate cancer PC3 cells: An iTRAQ-based proteomic analysis

Wenqin

et al. 2016

Life Sciences

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“…Untreated cells served as controls. The amount of intracellular ROS was expressed as the fold-increase of DCF fluorescence compared with the control [16]. The experiments were repeated three times.…”

Section: Measurement Of Ros Generationmentioning

confidence: 99%

Hepatocyte growth factor suppresses hypoxia/reoxygenation-induced XO activation in cardiac microvascular endothelial cells

Zhang

Chen

2014

Heart Vessels

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Hypoxia/reoxygenation (H/R) is one of the cellular stresses in pathological conditions, such as myocardial infarction, stroke and organ transplantation. Oxidative stress caused by reactive oxygen species (ROS) is a crucial element of H/R injury in vascular endothelial cells (ECs). Xanthine oxidase (XO) has been recognized to contribute to H/R injury. Of note, xanthine oxidoreductase is synthesized as xanthine dehydrogenase (XDH) and needs to be converted to XO to become a source of superoxide. Hepatocyte growth factor (HGF) has been found to protect ECs against H/R injury. The relation, however, between HGF and XO in ECs under H/R conditions remains to be determined. Primary cultured rat cardiac microvascular endothelial cells (CMECs) were exposed to 4 h of hypoxia and followed by 1 h of reoxygenation. Generation of ROS and cytosolic Ca2+ concentration was measured by flow cytometry qualification of DCFHDA and fluo-3 AM staining cells, respectively. XDH mRNA was qualified by qRT-PCR analysis. XO activity was determined by colorimetric assay and XO protein levels were determined by Western blot. Cell apoptosis was assessed by caspase-3 activity and Annexin V/PI staining. After H/R, cellular ROS production significantly increased. Both XO activity and XO protein increased after H/R. Cellular ROS elevation was inhibited by allopurinol (a potent XO inhibitor), indicting XO accounting for the generation of ROS after H/R. In addition, XDH mRNA increased after H/R, indicating a de novo XDH synthesis, which needs to be converted to XO to become a source of superoxide. Pretreatment of HGF inhibited the elevation of XO activity and XO protein level after H/R; however, HGF has no effect on the increase of XDH mRNA. We also find an increase of the cytosolic Ca2+ in CMECs after H/R. BAPTA-AM, a cell-permeable Ca2+ chelator, prevented the increase of XO activity and XO protein levels, implicating the elevated cytosolic Ca2+ concentration involvement in XO conversion and XO activation. HGF inhibited the elevation of cytosolic Ca2+ concentration in CMECs after H/R. Furthermore, HGF ameliorated H/R-induced CMECs apoptosis. These findings suggest a novel mechanism whereby HGF inhibited XO-generated ROS production after H/R treatment. H/R induces a de novo synthesis of XDH, the XO precursor. In addition, H/R increases cytosolic Ca2+ concentration and promotes a Ca2+ -involved XO conversion and XO activation. HGF has no effect on the increase of XDH mRNA; however, HGF inhibited the elevation of XO protein level and XO activity after H/R in the post-transcriptional level primarily by inhibiting the increase of cytosolic Ca2+ concentration. HGF protects CMECs from H/R-induced apoptosis by inhibiting the elevation of XO protein level and XO activity.

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Dihydroartemisinin Enhances Apo2L/TRAIL-Mediated Apoptosis in Pancreatic Cancer Cells via ROS-Mediated Up-Regulation of Death Receptor 5

Cited by 61 publications

References 52 publications

TRAIL Mediated Signaling in Pancreatic Cancer

TRAIL Mediated Signaling in Pancreatic Cancer

Mechanism of dihydroartemisinin-induced apoptosis in prostate cancer PC3 cells: An iTRAQ-based proteomic analysis

Hepatocyte growth factor suppresses hypoxia/reoxygenation-induced XO activation in cardiac microvascular endothelial cells

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