scholarly journals Alternol Sensitizes Renal Carcinoma Cells to TRAIL-Induced Apoptosis

2021 ◽  
Vol 12 ◽  
Author(s):  
Yu Ren ◽  
Xue Wang ◽  
Shuaishuai Huang ◽  
Yangkai Xu ◽  
Guobin Weng ◽  
...  
Keyword(s):  
Renal Carcinoma ◽  
Death Receptor ◽  
Annexin V ◽  
Carcinoma Cells ◽  
Luciferase Assay ◽  
Ros Generation ◽  
Antiapoptotic Proteins ◽  
Induced Apoptosis ◽  
Renal Carcinoma Cells

Purpose: Tumor necrosis factor–related apoptosis-inducing ligand (TRAIL), a member of the TNF family, can selectively induce cancer cell death while sparing normal cells. However, the application of TRAIL-based antitumor therapies has been hindered due to drug resistance. Alternol is a new compound isolated from microbial fermentation that possesses antitumor activity in different tumors. In our research, we discovered that alternol can sensitize TRAIL-induced apoptosis in renal carcinoma cells (RCCs).Materials and Methods: Cytotoxic activity was measured by MTT assay. Apoptosis was probed using the PI/annexin V method. Real-time PCR and western blot were used to test the levels of mRNA and protein, respectively. Luciferase assay was used to investigate whether CHOP regulated the expression of death receptor (DR) 5 through transcription. A xenogeneic tumor transplantation model was used to evaluate the anticancer effects of alternol/TRAIL in vivo.Results: When the mechanisms were investigated, we discovered that alternol increased DR5 expression. DR5 knockdown by siRNA eliminated the enhanced effect of alternol on TRAIL-mediated apoptosis. Alternol reduced the expression of antiapoptotic proteins and increased the levels of proapoptotic proteins. Moreover, alternol increased the level of CHOP, which is necessary for the enhancing effect of alternol on TRAIL-induced apoptosis, given that downregulation of CHOP abrogated the synergistic effect. DR5 upregulation induced by alternol required the production of reactive oxygen species (ROS). Removing ROS inhibited the induction of DR5 and blocked the antiapoptotic proteins induced by alternol.Conclusion: Taken together, our research suggested that alternol increased TRAIL-mediated apoptosis via inhibiting antiapoptotic proteins and upregulating DR5 levels via ROS generation and the CHOP pathway.

scholarly journals Cepharanthine Enhances TRAIL-Mediated Apoptosis Through STAMBPL1-Mediated Downregulation of Survivin Expression in Renal Carcinoma Cells

2018 ◽  
Vol 19 (10) ◽  
pp. 3280 ◽  
Author(s):  
Sk Shahriyar ◽  
Seon Woo ◽  
Seung Seo ◽  
Kyoung-jin Min ◽  
Taeg Kwon
Keyword(s):  
Renal Carcinoma ◽  
Apoptotic Cell ◽  
Combined Treatment ◽  
Ectopic Expression ◽  
Survivin Expression ◽  
Carcinoma Cells ◽  
Inhibitory Protein ◽  
Anticancer Properties ◽  
Induced Apoptosis ◽  
Renal Carcinoma Cells

Cepharanthine (CEP) is a natural plant alkaloid, and has anti-inflammatory, antineoplastic, antioxidative and anticancer properties. In this study, we investigated whether CEP could sensitize renal carcinoma Caki cells to tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)-induced apoptosis. CEP alone and TRAIL alone had no effect on apoptosis. However, combined CEP and TRAIL treatment markedly enhanced apoptotic cell death in cancer cells, but not in normal cells. CEP induced downregulation of survivin and cellular-FLICE inhibitory protein (c-FLIP) expression at post-translational levels. Ectopic expression of survivin blocked apoptosis by combined treatment with CEP plus TRAIL, but not in c-FLIP overexpression. Interestingly, CEP induced survivin downregulation through downregulation of deubiquitin protein of STAM-binding protein-like 1 (STAMBPL1). Overexpression of STAMBPL1 markedly recovered CEP-mediated survivin downregulation. Taken together, our study suggests that CEP sensitizes TRAIL-mediated apoptosis through downregulation of survivin expression at the post-translational levels in renal carcinoma cells.

scholarly journals A Novel High-Throughput Technique for Identifying Monoclonal Antibodies capable of Death Receptor Induced Apoptosis

2009 ◽  
Vol 2 ◽  
pp. JCD.S3660
Author(s):  
Hang Fai Kwok ◽  
Julie A. Gormley ◽  
Christopher J. Scott ◽  
James A. Johnston ◽  
Shane A. Olwill
Keyword(s):  
Cell Death ◽  
High Throughput ◽  
High Throughput Screening ◽  
False Negative ◽  
Death Receptor ◽  
Annexin V ◽  
Fas Receptor ◽  
Induced Apoptosis

The study of death receptor family induced apoptosis has gained momentum in recent years with the knowledge that therapeutic antibodies targeting DR4 and DR5 (death receptor's 4 and 5) have proved efficacious in multiple clinical trials. The therapeutic rationale is based on targeting and amplifying a tumour tissues normal cell death programme (apoptosis). While advances in the targeting of DR4 and DR5 have been successful the search for an agonistic antibody to another family member, the Fas receptor, has proven more elusive. This is partly due to the differing in vitro and in vivo characteristics of individual antibodies. In order to induce Fas targeted cell death an antibody must be capable of binding to and trimerising the receptor. It has been shown that antibodies capable of performing this function in vivo, with the assistance of tumour associated cells, do not always induce apoptosis in vitro. As a result the use of current methodologies to detect functional antibodies in vitro may have dismissed potential therapeutic candidates ('false negative'). Here we report a novel high throughput screening technique which artificially cross-links antibodies bound to the Fas receptor. By combining this process with Annexin-V and Prodidium Iodide (PI) staining we can select for antibodies which have the potential to induce apoptosis in vivo.

Endoplasmic reticulum stress mediates withaferin A-induced apoptosis in human renal carcinoma cells

2011 ◽  
Vol 25 (3) ◽  
pp. 692-698 ◽  
Author(s):  
Min Jung Choi ◽  
Eun Jung Park ◽  
Kyoung Jin Min ◽  
Jong-Wook Park ◽  
Taeg Kyu Kwon
Keyword(s):  
Endoplasmic Reticulum ◽  
Endoplasmic Reticulum Stress ◽  
Renal Carcinoma ◽  
Carcinoma Cells ◽  
Withaferin A ◽  
Induced Apoptosis ◽  
Human Renal Carcinoma ◽  
Renal Carcinoma Cells

scholarly journals NPRL-Z-1, as a New Topoisomerase II Poison, Induces Cell Apoptosis and ROS Generation in Human Renal Carcinoma Cells

PLoS ONE ◽  
2014 ◽  
Vol 9 (11) ◽  
pp. e112220 ◽  
Author(s):  
Szu-Ying Wu ◽  
Shiow-Lin Pan ◽  
Zhi-Yan Xiao ◽  
Jui-Ling Hsu ◽  
Mei-Chuan Chen ◽  
...  
Keyword(s):  
Cell Apoptosis ◽  
Topoisomerase Ii ◽  
Renal Carcinoma ◽  
Carcinoma Cells ◽  
Ros Generation ◽  
Human Renal Carcinoma ◽  
Renal Carcinoma Cells

scholarly journals Berberine associated photodynamic therapy promotes autophagy and apoptosis via ROS generation in renal carcinoma cells

2020 ◽  
Vol 123 ◽  
pp. 109794 ◽  
Author(s):  
Tairine Zara Lopes ◽  
Fabio Rogério de Moraes ◽  
Antonio Claudio Tedesco ◽  
Raghuvir Krishnaswamy Arni ◽  
Paula Rahal ◽  
...  
Keyword(s):  
Photodynamic Therapy ◽  
Renal Carcinoma ◽  
Carcinoma Cells ◽  
Ros Generation ◽  
Renal Carcinoma Cells

scholarly journals Metallothionein 3 Is a Hypoxia-Upregulated Oncogene Enhancing Cell Invasion and Tumorigenesis in Human Bladder Carcinoma Cells

2019 ◽  
Vol 20 (4) ◽  
pp. 980 ◽  
Author(s):  
Ke-Hung Tsui ◽  
Chen-Pang Hou ◽  
Kang-Shuo Chang ◽  
Yu-Hsiang Lin ◽  
Tsui-Hsia Feng ◽  
...  
Keyword(s):  
Bladder Carcinoma ◽  
Annexin V ◽  
Carcinoma Cells ◽  
Gene Expressions ◽  
T24 Cells ◽  
Apoptosis Assay ◽  
Induced Apoptosis ◽  
Bladder Carcinoma Cells

Metallothioneins have been viewed as modulators in a number of biological regulations regarding cancerous development; however, the function of metallothionein 3 (MT3) in bladder cancer is unexplored. We determined the regulatory mechanisms and potential function of MT3 in bladder carcinoma cells. Real-Time Reverse Transcriptase-Polymerase Chain Reaction (RT-qPCR) assays revealed that TSGH-8301 cells expressed more MT3 levels than RT-4, HT1376, and T24 cells. Immunoblot and RT-qPCR assays showed that arsenic (AS2O3) treatments enhanced the gene expression of MT3. Hypoxia induced HIF-1α, HIF-2α, and MT3 expression; furthermore, HIF-2α-knockdown attenuated hypoxic activation on MT3 expression. Ectopic overexpression of MT3 increased cell proliferation, invasion, and tumorigenesis significantly in T24 and HT1376 cells in vitro and in vivo; however, MT3-knockdown in TSGH-8301 cells had the reverse effect. Moreover, knockdown of MT3 enhanced arsenic-induced apoptosis determined by the Annexin V-FITC apoptosis assay. MT3-overexpression downregulated the gene expressions of N-myc downstream regulated gene 1 (NDRG1), N-myc downstream regulated gene 2 (NDRG2), and the mammary serine protease inhibitor (MASPIN) in HT1376 and T24 cells, whereas MT3-knockdown in TSGH-8301 cells had the opposite effect. The experiments indicated that MT3 is an arsenic- and hypoxia-upregulated oncogene that promotes cell growth and invasion of bladder carcinoma cells via downregulation of NDRG1, NDRG2, and MASPIN expressions.

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