The tumor suppressive effect and apoptotic mechanism of TRAIL gene‐containing recombinant NDV in TRAIL‐resistant colorectal cancer HT‐29 cells and TRAIL‐nonresistant HCT116 cells, with each cell bearing a mouse model
Abstract Background TRAIL is an anticancer drug that induces cancer cell apoptosis by interacting with death receptors (DRs). However, owing to low cell‐surface expression of DRs, certain colorectal cancer (CRC) cells resist TRAIL‐induced apoptosis. Newcastle disease virus (NDV) infection can elevat...
| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
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Wiley
2023-10-01
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| Series: | Cancer Medicine |
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| Online Access: | https://doi.org/10.1002/cam4.6622 |
| _version_ | 1797626675190562816 |
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| author | Bo‐Kyoung Jung Yong Hee An Sung Hoon Jang Gyoungah Ryu Saet‐byel Jung Seonhee Kim Cuk‐Seong Kim Hyun Jang |
| author_facet | Bo‐Kyoung Jung Yong Hee An Sung Hoon Jang Gyoungah Ryu Saet‐byel Jung Seonhee Kim Cuk‐Seong Kim Hyun Jang |
| author_sort | Bo‐Kyoung Jung |
| collection | DOAJ |
| description | Abstract Background TRAIL is an anticancer drug that induces cancer cell apoptosis by interacting with death receptors (DRs). However, owing to low cell‐surface expression of DRs, certain colorectal cancer (CRC) cells resist TRAIL‐induced apoptosis. Newcastle disease virus (NDV) infection can elevate DR protein expression in cancer cells, potentially influencing their TRAIL sensitivity. However, the precise mechanism by which NDV infection modulates DR expression and impacts TRAIL sensitivity in cancer cells remains unknown. Methods Herein, we developed nonpathogenic NDV VG/GA strain‐based recombinant NDV (rNDV) and TRAIL gene‐containing rNDV (rNDV‐TRAIL). We observed that viral infections lead to increased DR and TRAIL expressions and activate signaling proteins involved in intrinsic and extrinsic apoptosis pathways. Experiments were conducted in vitro using TRAIL‐resistant CRC cells (HT‐29) and nonresistant CRC cells (HCT116) and in vivo using relevant mouse models. Results rNDV‐TRAIL was found to exhibit better apoptotic efficacy than rNDV in CRC cells. Notably, rNDV‐TRAIL had the stronger cancer cell‐killing effect in TRAIL‐resistant CRC cells. Western blot analyses showed that both rNDV and rNDV‐TRAIL infections activate signaling proteins involved in the intrinsic and extrinsic apoptotic pathways. Notably, rNDV‐TRAIL promotes concurrent intrinsic and extrinsic signal transduction in both HCT‐116 and HT‐29 cells. Conclusions Therefore, rNDV‐TRAIL infection effectively enhances DR expression in DR‐depressed HT‐29 cells. Moreover, the TRAIL protein expressed by rNDV‐TRAIL effectively interacts with DR, leading to enhanced apoptosis in TRAIL‐resistant HT‐29 cells. Therefore, rNDV‐TRAIL has potential as a promising therapeutic approach for treating TRAIL‐resistant cancers. |
| first_indexed | 2024-03-11T10:13:33Z |
| format | Article |
| id | doaj.art-28d148d00a424ef3bcbd183e7b7ec3e4 |
| institution | Directory Open Access Journal |
| issn | 2045-7634 |
| language | English |
| last_indexed | 2024-03-11T10:13:33Z |
| publishDate | 2023-10-01 |
| publisher | Wiley |
| record_format | Article |
| series | Cancer Medicine |
| spelling | doaj.art-28d148d00a424ef3bcbd183e7b7ec3e42023-11-16T12:08:59ZengWileyCancer Medicine2045-76342023-10-011220203802039510.1002/cam4.6622The tumor suppressive effect and apoptotic mechanism of TRAIL gene‐containing recombinant NDV in TRAIL‐resistant colorectal cancer HT‐29 cells and TRAIL‐nonresistant HCT116 cells, with each cell bearing a mouse modelBo‐Kyoung Jung0Yong Hee An1Sung Hoon Jang2Gyoungah Ryu3Saet‐byel Jung4Seonhee Kim5Cuk‐Seong Kim6Hyun Jang7Libentech Co. LTD Daejeon Republic of KoreaLibentech Co. LTD Daejeon Republic of KoreaGraduate School of Medical Science, College of medicine Yonsei University Seoul Republic of KoreaLibentech Co. LTD Daejeon Republic of KoreaLibentech Co. LTD Daejeon Republic of KoreaDepartment of Physiology & Medical Science, College of Medicine Chungnam National University Daejeon Republic of KoreaDepartment of Physiology & Medical Science, College of Medicine Chungnam National University Daejeon Republic of KoreaLibentech Co. LTD Daejeon Republic of KoreaAbstract Background TRAIL is an anticancer drug that induces cancer cell apoptosis by interacting with death receptors (DRs). However, owing to low cell‐surface expression of DRs, certain colorectal cancer (CRC) cells resist TRAIL‐induced apoptosis. Newcastle disease virus (NDV) infection can elevate DR protein expression in cancer cells, potentially influencing their TRAIL sensitivity. However, the precise mechanism by which NDV infection modulates DR expression and impacts TRAIL sensitivity in cancer cells remains unknown. Methods Herein, we developed nonpathogenic NDV VG/GA strain‐based recombinant NDV (rNDV) and TRAIL gene‐containing rNDV (rNDV‐TRAIL). We observed that viral infections lead to increased DR and TRAIL expressions and activate signaling proteins involved in intrinsic and extrinsic apoptosis pathways. Experiments were conducted in vitro using TRAIL‐resistant CRC cells (HT‐29) and nonresistant CRC cells (HCT116) and in vivo using relevant mouse models. Results rNDV‐TRAIL was found to exhibit better apoptotic efficacy than rNDV in CRC cells. Notably, rNDV‐TRAIL had the stronger cancer cell‐killing effect in TRAIL‐resistant CRC cells. Western blot analyses showed that both rNDV and rNDV‐TRAIL infections activate signaling proteins involved in the intrinsic and extrinsic apoptotic pathways. Notably, rNDV‐TRAIL promotes concurrent intrinsic and extrinsic signal transduction in both HCT‐116 and HT‐29 cells. Conclusions Therefore, rNDV‐TRAIL infection effectively enhances DR expression in DR‐depressed HT‐29 cells. Moreover, the TRAIL protein expressed by rNDV‐TRAIL effectively interacts with DR, leading to enhanced apoptosis in TRAIL‐resistant HT‐29 cells. Therefore, rNDV‐TRAIL has potential as a promising therapeutic approach for treating TRAIL‐resistant cancers.https://doi.org/10.1002/cam4.6622apoptosiscolorectal cancerviral infectionviral oncology |
| spellingShingle | Bo‐Kyoung Jung Yong Hee An Sung Hoon Jang Gyoungah Ryu Saet‐byel Jung Seonhee Kim Cuk‐Seong Kim Hyun Jang The tumor suppressive effect and apoptotic mechanism of TRAIL gene‐containing recombinant NDV in TRAIL‐resistant colorectal cancer HT‐29 cells and TRAIL‐nonresistant HCT116 cells, with each cell bearing a mouse model Cancer Medicine apoptosis colorectal cancer viral infection viral oncology |
| title | The tumor suppressive effect and apoptotic mechanism of TRAIL gene‐containing recombinant NDV in TRAIL‐resistant colorectal cancer HT‐29 cells and TRAIL‐nonresistant HCT116 cells, with each cell bearing a mouse model |
| title_full | The tumor suppressive effect and apoptotic mechanism of TRAIL gene‐containing recombinant NDV in TRAIL‐resistant colorectal cancer HT‐29 cells and TRAIL‐nonresistant HCT116 cells, with each cell bearing a mouse model |
| title_fullStr | The tumor suppressive effect and apoptotic mechanism of TRAIL gene‐containing recombinant NDV in TRAIL‐resistant colorectal cancer HT‐29 cells and TRAIL‐nonresistant HCT116 cells, with each cell bearing a mouse model |
| title_full_unstemmed | The tumor suppressive effect and apoptotic mechanism of TRAIL gene‐containing recombinant NDV in TRAIL‐resistant colorectal cancer HT‐29 cells and TRAIL‐nonresistant HCT116 cells, with each cell bearing a mouse model |
| title_short | The tumor suppressive effect and apoptotic mechanism of TRAIL gene‐containing recombinant NDV in TRAIL‐resistant colorectal cancer HT‐29 cells and TRAIL‐nonresistant HCT116 cells, with each cell bearing a mouse model |
| title_sort | tumor suppressive effect and apoptotic mechanism of trail gene containing recombinant ndv in trail resistant colorectal cancer ht 29 cells and trail nonresistant hct116 cells with each cell bearing a mouse model |
| topic | apoptosis colorectal cancer viral infection viral oncology |
| url | https://doi.org/10.1002/cam4.6622 |
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