Newly synthesized quinazolinone HMJ-38 suppresses angiogenetic responses and triggers human umbilical vein endothelial cell apoptosis through p53-modulated Fas/death receptor signaling

Chiang, Jen‐Huai; Yang, Jai Sing; Lu, Chi‐Cheng; Hour, Mann Jen; Chang, Sun‐Yran; Lee, Tsung‐Han; Chung, Jing Gung

doi:10.1016/j.taap.2013.03.007

Cited by 43 publications

(70 citation statements)

References 64 publications

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“…Then the cells were collected andfixed in 75% ethanol overnight at -20˚C before being stained with 0.1 M phosphate/citric acid buffer (0.2 M NaHPO 4 and 0.1 M citric acid, pH 7.8) and 40 µg/ml PI for 30 min at room temperature in the dark. The cells were determined with BD FACSCalibur (BD Biosciences, Franklin Lakes, NJ, USA) as previously described (6).…”

Section: Chemicals and Reagentsmentioning

confidence: 99%

“…Mitochondrial permeability can be regulated to release various apoptotic factors such as cytochrome c, Apaf-1 and pro-caspase-9 to cytosol to form apoptosome and to activate the downstream of caspase-9 (6,7). The membrane death receptors (extrinsic apoptotic pathway) located in the membrane include Fas/ CD95, death receptor 4 (DR4) and DR5 that can influence the distal executioner caspases (6). In addition, reactive oxygen species (ROS) production and DNA damage caused by anticancer drugs lead to an increase of phosphorylation of ataxia-telangiectasia-mutated kinase (ATM) and p53 to trigger human cancer cell apoptosis (8).…”

Section: Introductionmentioning

confidence: 99%

“…p53 phosphorylation on the residue of Ser15 has been linked to apoptosis and shown to be a transcription factor to modulate apoptotic target genes such as Fas and DR5 (9). p53 gene expression has been shown to upregulate both the extrinsic and the intrinsic apoptotic signaling pathways (6,10).…”

Section: Introductionmentioning

confidence: 99%

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Kaempferol induces ATM/p53-mediated death receptor and mitochondrial apoptosis in human umbilical vein endothelial cells

Lee

Yang

Tsai

et al. 2016

International Journal of Oncology

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Abstract. Kaempferol is a member of the flavonoid compounds found in vegetables and fruits. It is shown to exhibit biological impact and anticancer activity, but no report exists on the angiogenic effect of kaempferol and induction of cell apoptosis in vitro. In this study, we investigated the role of kaempferol on anti-angiogenic property and the apoptotic mechanism of human umbilical vein endothelial cells (HUVECs). Our results demonstrated that kaempferol decreased HUVEC viability in a time-and concentration-dependent manner. Kaempferol also induced morphological changes and sub-G1 phase cell population (apoptotic cells). Kaempferol triggered apoptosis of HUVECs as detecting by DNA fragmentation, comet assay and immunofluorescent staining for activated caspase-3. The caspase signals, including caspase-8, -9 and -3, were time-dependently activated in HUVECs after kaempferol exposure. Furthermore, pre-treatment with a specific inhibitor of caspase-8 (Z-IETD-FMK) significantly reduced the activity of caspase-8, -9 and -3, indicating that extrinsic pathway is a major signaling pathway in kaempferoltreated HUVECs. Importantly, kaempferol promoted reactive oxygen species (ROS) evaluated using flow cytometric assay in HUVECs. We further investigated the upstream extrinsic pathway and showed that kaempferol stimulated death receptor signals [Fas/CD95, death receptor 4 (DR4) and DR5] through increasing the levels of phosphorylated p53 and phosphorylated ATM pathways in HUVECs, which can be individually confirmed by N-acetylcysteine (NAC), ATM specific inhibitor (caffeine) and p53 siRNA. Based on these results, kaempferol-induced HUVEC apoptosis was involved in an ROS-mediated p53/ATM/death receptor signaling. Kaempferol might possess therapeutic effects on cancer treatment in anti-vascular targeting.

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Section: Chemicals and Reagentsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Kaempferol induces ATM/p53-mediated death receptor and mitochondrial apoptosis in human umbilical vein endothelial cells

Lee

Yang

Tsai

et al. 2016

International Journal of Oncology

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“…cDNAs were synthesized from each RNA sample, as previously reported (37,38). Subsequent qPCR for each sample was performed using an Applied Biosystems 7300 Real-Time PCR system (Applied Biosystems; Thermo Fisher Scientific, Inc., Waltham, MA, USA) according to the manufacturer's instructions.…”

Section: Reverse Transcription Quantitative Polymerase Chain Reactionmentioning

confidence: 99%

“…Following treatment, the whole cell lysate was collected, and immunoblotting was performed to determine the protein expression levels, as detailed by Chen et al (36). The protein signals were detected using an Immobilon Western Chemiluminescent HRP Substrate kit (Merck Millipore, Billerica, MA, USA) and Bio-MAX MR X-ray film (Eastman Kodak, Rochester, NY, USA), as previously described (37,38).…”

Section: Reverse Transcription Quantitative Polymerase Chain Reactionmentioning

confidence: 99%

Inhibitory effects of tetrandrine on epidermal growth factor-induced invasion and migration in HT29 human colorectal adenocarcinoma cells

Horng

Yang

Chiang³

et al. 2015

Molecular Medicine Reports

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Abstract.Tetrandrine has been shown to reduce cancer cell proliferation and to inhibit metastatic effects in multiple cancer models in vitro and in vivo. However, the effects of tetrandrine on the underlying mechanism of HT29 human colorectal adenocarcinoma cell metastasis remain to be fully elucidated. The aim of the present study was focused on tetrandrine-treated HT29 cells following epidermal growth factor (EGF) treatment, and Transwell, gelatin zymography, gene expression and immunoblotting assays were performed to investigate metastatic effects in vitro. Tetrandrine was observed to dose-dependently inhibit EGF-induced HT29 cell invasion and migration, however, no effect on cell viability occurred following exposure to tetradrine between 0.5 and 2 µM. Tetrandrine treatment inhibited the enzymatic activity of matrix metalloprotease (MMP)-2 and MMP-9 in a concentration-dependent manner. The present study also found a reduction in the mRNA expression levels of MMP-2 and MMP-9 in the tetrandrine-treated HT29 cells. Tetrandrine also suppressed the phosphorylation of EGF receptor (EGFR) and its downstream pathway, including phosphoinositide-dependent kinase 1, phosphatidylinositol 3-kinase and phosphorylated AKT, suppressing the gene expression of MMP-2 and MMP-9. Furthermore, tetrandrine triggered mitogen-activated protein kinase signaling through the suppressing the activation of phosphorylated extracellular signal-regulated protein kinase. These data suggested that targeting EGFR signaling and its downstream molecules contributed to the inhibition of EGF-induced HT29 cell metastasis caused by tetrandrine, eventually leading to a reduction in the mRNA and gelatinase activities of MMP-2 and MMP-9, respectively. IntroductionEpidermal growth factor receptor (EGFR) is a member of the ErbB family of receptor tyrosine kinases (1), and EGFR activation by ligand binding stimulates multiple signals, including phosphatidylinositol 3-kinase (PI3K)/AKT, mitogen-activated protein kinases (MAPKs) and nuclear factor-κB pathways, ultimately resulting in cellular proliferation, survival, angiogenesis invasion and metastasis (2,3). Abnormal protein activity and/or expression levels of EGFR have been correlated with the etiology of several types of human cancer, including colorectal cancer (4,5), non-small cell lung cancer (6,7), breast cancer (8,9), head and neck squamous cell carcinoma (10,11), pancreatic cancer (12) and brain cancer (13). EGFR-targeted therapy has been validated in human colorectal cancer (14), and the chemotherapeutics include pharmacological agents, including cetuximab (Erbitux), which is an EGFR inhibitor (15). EGFR acts to bind an EGFR-selective ligand activated by epidermal growth factor (EGF), transforming growth factor-α, amphiregulin or neuregulin, finally leading to cell proliferation, invasion and the inhibition of apoptosis (15)(16)(17).Tetrandrine is a bisbenzylisoquinoline alkaloid, which is isolated from the dried root of Stephania tetrandra of the

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Ursolic acid triggers nonprogrammed death (necrosis) in human glioblastoma multiforme DBTRG‐05MG cells through MPT pore opening and ATP decline

Huang

Liao

et al. 2014

Molecular Nutrition Food Res

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Newly synthesized quinazolinone HMJ-38 suppresses angiogenetic responses and triggers human umbilical vein endothelial cell apoptosis through p53-modulated Fas/death receptor signaling

Cited by 43 publications

References 64 publications

Kaempferol induces ATM/p53-mediated death receptor and mitochondrial apoptosis in human umbilical vein endothelial cells

Kaempferol induces ATM/p53-mediated death receptor and mitochondrial apoptosis in human umbilical vein endothelial cells

Inhibitory effects of tetrandrine on epidermal growth factor-induced invasion and migration in HT29 human colorectal adenocarcinoma cells

Ursolic acid triggers nonprogrammed death (necrosis) in human glioblastoma multiforme DBTRG‐05MG cells through MPT pore opening and ATP decline

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