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Published on: November 11, 2016
IPS-1 plays a dual function to directly induce apoptosis in murine melanoma cells by inactivated Sendai virus
Quan Zhang1, Xiaoshuang Xu, Yan Yuan
1Comparative Medicine Center, College of Veterinary Medicine, Yangzhou University, Yangzhou, China.
Abstract:
Inactivated Sendai virus (HVJ-E) directly kills cancer cells by inducing apoptosis through a mechanism mediated by Janus kinases/signal transducers and activators of transcription (JAK/STAT) signaling pathways. However, whether other signaling pathways are involved remain largely unknown. This study aimed to investigate the mechanism underlying HVJ-E-induced apoptosis in murine B16F10 melanoma cells. We found that HVJ-E induced B16F10 cell apoptosis via the caspase pathway, particularly caspase-9, which mediates the intrinsic apoptotic pathway. Mitogen-activated protein kinase (MAPK) pathway activation also contributed to HVJ-E-induced apoptosis. Whereas caspase pathway involvement depended on both IFN-β promoter stimulator-1 (IPS-1) and type I interferon (IFN), MAPK pathway activation was independent of type I IFN but involved IPS-1. In addition, intratumoral HVJ-E treatment displayed a direct oncolytic effect in an in vivo BALB/c nude mouse melanoma model. Collectively, our data provides new insights into the mechanism underlying HVJ-E-induced apoptosis in tumor cells.
Insights
Inactivated Sendai virus (HVJ-E) triggers apoptosis in melanoma cells via caspase and MAPK pathways. Intratumoral HVJ-E treatment showed direct oncolytic effects in mice.
Area of Science:
- Oncology
- Virology
- Cell Biology
Background:
- Inactivated Sendai virus (HVJ-E) induces apoptosis in cancer cells via JAK/STAT pathways.
- The precise molecular mechanisms of HVJ-E-induced apoptosis involving other signaling pathways are not fully understood.
Purpose of the Study:
- To investigate the signaling pathways mediating apoptosis induced by HVJ-E in murine B16F10 melanoma cells.
- To elucidate the role of intrinsic apoptotic pathways and MAPK signaling in HVJ-E's oncolytic mechanism.
Main Methods:
- Treatment of B16F10 melanoma cells with HVJ-E.
- Analysis of apoptosis induction via caspase and MAPK pathways.
- Assessment of the involvement of IFN-β promoter stimulator-1 (IPS-1) and type I interferon (IFN).
- In vivo studies using a murine melanoma model (BALB/c nude mice).
Main Results:
- HVJ-E induced apoptosis in B16F10 cells through the caspase pathway, specifically involving caspase-9 (intrinsic apoptosis).
- Mitogen-activated protein kinase (MAPK) pathway activation also contributed to HVJ-E-induced apoptosis.
- Caspase pathway activation was dependent on IPS-1 and type I IFN, while MAPK activation was IPS-1 dependent but type I IFN independent.
- Intratumoral HVJ-E administration demonstrated direct oncolytic activity in a mouse melanoma model.
Conclusions:
- HVJ-E induces melanoma cell apoptosis via both intrinsic caspase-dependent and MAPK-dependent pathways.
- The study reveals distinct dependencies on IPS-1 and type I IFN for these pathways.
- HVJ-E exhibits direct oncolytic potential, offering insights into its therapeutic application for melanoma.
Related Concept Videos
The Intrinsic Apoptotic Pathway
The Extrinsic Apoptotic Pathway
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