Curcumin Sensitizes Kidney Cancer Cells to TRAIL-Induced Apoptosis via ROS Mediated Activation of JNK-CHOP Pathway and Upregulation of DR4
Tumour necrosis factor-related apoptosis-inducing ligand (TRAIL), is a selective anticancer cytokine capable of exerting a targeted therapy approach. Disappointingly, recent research has highlighted the development of TRAIL resistance in cancer cells, thus minimising its usefulness in clinical setti...
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2020-05-01
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| author | Ismael Obaidi Hilary Cassidy Verónica Ibáñez Gaspar Jasmin McCaul Michael Higgins Melinda Halász Alison L. Reynolds Breandan N. Kennedy Tara McMorrow |
| author_facet | Ismael Obaidi Hilary Cassidy Verónica Ibáñez Gaspar Jasmin McCaul Michael Higgins Melinda Halász Alison L. Reynolds Breandan N. Kennedy Tara McMorrow |
| author_sort | Ismael Obaidi |
| collection | DOAJ |
| description | Tumour necrosis factor-related apoptosis-inducing ligand (TRAIL), is a selective anticancer cytokine capable of exerting a targeted therapy approach. Disappointingly, recent research has highlighted the development of TRAIL resistance in cancer cells, thus minimising its usefulness in clinical settings. However, several recent studies have demonstrated that cancer cells can be sensitised to TRAIL through the employment of a combinatorial approach, utilizing TRAIL in conjunction with other natural or synthetic anticancer agents. In the present study, the chemo-sensitising effect of curcumin on TRAIL-induced apoptosis in renal carcinoma cells (RCC) was investigated. The results indicate that exposure of kidney cancer ACHN cells to curcumin sensitised the cells to TRAIL, with the combination treatment of TRAIL and curcumin synergistically targeting the cancer cells without affecting the normal renal proximal tubular epithelial cells (RPTEC/TERT1) cells. Furthermore, this combination treatment was shown to induce caspase-dependent apoptosis, inhibition of the proteasome, induction of ROS, upregulation of death receptor 4 (DR4), alterations in mitogen-activated protein kinase (MAPK) signalling and induction of endoplasmic reticulum stress. An in vivo zebrafish embryo study demonstrated the effectiveness of the combinatorial regime to inhibit tumour formation without affecting zebrafish embryo viability or development. Overall, the results arising from this study demonstrate that curcumin has the ability to sensitise TRAIL-resistant ACHN cells to TRAIL-induced apoptosis. |
| first_indexed | 2024-03-10T20:06:04Z |
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| issn | 2079-7737 |
| language | English |
| last_indexed | 2024-03-10T20:06:04Z |
| publishDate | 2020-05-01 |
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| series | Biology |
| spelling | doaj.art-f944a414d26c4c7c980fb77003f86a8e2023-11-19T23:17:20ZengMDPI AGBiology2079-77372020-05-01959210.3390/biology9050092Curcumin Sensitizes Kidney Cancer Cells to TRAIL-Induced Apoptosis via ROS Mediated Activation of JNK-CHOP Pathway and Upregulation of DR4Ismael Obaidi0Hilary Cassidy1Verónica Ibáñez Gaspar2Jasmin McCaul3Michael Higgins4Melinda Halász5Alison L. Reynolds6Breandan N. Kennedy7Tara McMorrow8NIBRT|National Institute for Bioprocessing, Research and Training, Foster Avenue, Mount Merrion, Blackrock, Co., A94 X099 Dublin, IrelandUCD Centre for Toxicology, School of Biomedical and Biomolecular Sciences, Conway Institute, University College Dublin, 4 Dublin, IrelandUCD Centre for Toxicology, School of Biomedical and Biomolecular Sciences, Conway Institute, University College Dublin, 4 Dublin, IrelandUCD Centre for Toxicology, School of Biomedical and Biomolecular Sciences, Conway Institute, University College Dublin, 4 Dublin, IrelandUCD Centre for Toxicology, School of Biomedical and Biomolecular Sciences, Conway Institute, University College Dublin, 4 Dublin, IrelandSystems Biology Ireland, School of Medicine, University College Dublin, Belfield, 4 Dublin, IrelandUCD Centre for Toxicology, School of Biomedical and Biomolecular Sciences, Conway Institute, University College Dublin, 4 Dublin, IrelandUCD Centre for Toxicology, School of Biomedical and Biomolecular Sciences, Conway Institute, University College Dublin, 4 Dublin, IrelandUCD Centre for Toxicology, School of Biomedical and Biomolecular Sciences, Conway Institute, University College Dublin, 4 Dublin, IrelandTumour necrosis factor-related apoptosis-inducing ligand (TRAIL), is a selective anticancer cytokine capable of exerting a targeted therapy approach. Disappointingly, recent research has highlighted the development of TRAIL resistance in cancer cells, thus minimising its usefulness in clinical settings. However, several recent studies have demonstrated that cancer cells can be sensitised to TRAIL through the employment of a combinatorial approach, utilizing TRAIL in conjunction with other natural or synthetic anticancer agents. In the present study, the chemo-sensitising effect of curcumin on TRAIL-induced apoptosis in renal carcinoma cells (RCC) was investigated. The results indicate that exposure of kidney cancer ACHN cells to curcumin sensitised the cells to TRAIL, with the combination treatment of TRAIL and curcumin synergistically targeting the cancer cells without affecting the normal renal proximal tubular epithelial cells (RPTEC/TERT1) cells. Furthermore, this combination treatment was shown to induce caspase-dependent apoptosis, inhibition of the proteasome, induction of ROS, upregulation of death receptor 4 (DR4), alterations in mitogen-activated protein kinase (MAPK) signalling and induction of endoplasmic reticulum stress. An in vivo zebrafish embryo study demonstrated the effectiveness of the combinatorial regime to inhibit tumour formation without affecting zebrafish embryo viability or development. Overall, the results arising from this study demonstrate that curcumin has the ability to sensitise TRAIL-resistant ACHN cells to TRAIL-induced apoptosis.https://www.mdpi.com/2079-7737/9/5/92TRAILcurcuminchemosensitisationapoptosiszebrafishROS |
| spellingShingle | Ismael Obaidi Hilary Cassidy Verónica Ibáñez Gaspar Jasmin McCaul Michael Higgins Melinda Halász Alison L. Reynolds Breandan N. Kennedy Tara McMorrow Curcumin Sensitizes Kidney Cancer Cells to TRAIL-Induced Apoptosis via ROS Mediated Activation of JNK-CHOP Pathway and Upregulation of DR4 Biology TRAIL curcumin chemosensitisation apoptosis zebrafish ROS |
| title | Curcumin Sensitizes Kidney Cancer Cells to TRAIL-Induced Apoptosis via ROS Mediated Activation of JNK-CHOP Pathway and Upregulation of DR4 |
| title_full | Curcumin Sensitizes Kidney Cancer Cells to TRAIL-Induced Apoptosis via ROS Mediated Activation of JNK-CHOP Pathway and Upregulation of DR4 |
| title_fullStr | Curcumin Sensitizes Kidney Cancer Cells to TRAIL-Induced Apoptosis via ROS Mediated Activation of JNK-CHOP Pathway and Upregulation of DR4 |
| title_full_unstemmed | Curcumin Sensitizes Kidney Cancer Cells to TRAIL-Induced Apoptosis via ROS Mediated Activation of JNK-CHOP Pathway and Upregulation of DR4 |
| title_short | Curcumin Sensitizes Kidney Cancer Cells to TRAIL-Induced Apoptosis via ROS Mediated Activation of JNK-CHOP Pathway and Upregulation of DR4 |
| title_sort | curcumin sensitizes kidney cancer cells to trail induced apoptosis via ros mediated activation of jnk chop pathway and upregulation of dr4 |
| topic | TRAIL curcumin chemosensitisation apoptosis zebrafish ROS |
| url | https://www.mdpi.com/2079-7737/9/5/92 |
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