Dataset Information

Recombinant measles virus vaccine rMV-Hu191 exerts an oncolytic effect on esophageal squamous cell carcinoma via caspase-3/GSDME-mediated pyroptosis.

ABSTRACT: Oncolytic viruses have recently been proven to be an effective and promising cancer therapeutic strategy, but there is rare data about oncolytic therapy in esophageal squamous cell carcinoma (ESCC), especially oncolytic measles virotherapy. Therefore, this study aimed to explore whether the recombinant measles virus vaccine strain rMV-Hu191 has an oncolytic effect against ESCC cells in vitro and in vivo and elucidate the underlying mechanisms. Our results showed that rMV-Hu191 could efficiently replicate in and kill ESCC cells through caspase-3/GSDME-mediated pyroptosis. Mechanistically, rMV-Hu191 triggers mitochondrial dysfunction to induce pyroptosis, which is mediated by BAK (BCL2 antagonist/killer 1) or BAX (BCL2 associated X). Further analysis revealed that rMV-Hu191 activates inflammatory signaling in ESCC cells, which may enhance the oncolytic efficiency. Moreover, intratumoral injection of rMV-Hu191 induced dramatic tumor regression in an ESCC xenograft model. Collectively, these findings imply that rMV-Hu191 exhibits an antitumor effect through BAK/BAX-dependent caspase-3/GSDME-mediated pyroptosis and provides a potentially promising new therapy for ESCC treatment.

SUBMITTER: Wu A

PROVIDER: S-EPMC10195838 | biostudies-literature | 2023 May

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Recombinant measles virus vaccine rMV-Hu191 exerts an oncolytic effect on esophageal squamous cell carcinoma via caspase-3/GSDME-mediated pyroptosis.

Wu Ailing A Li Zhongyue Z Wang Yilong Y Chen Yi Y Peng Jinkai J Zhu Mengying M Li Yueyue Y Song Hai H Zhou Dongming D Zhang Chudi C Lv Yao Y Zhao Zhengyan Z

Cell death discovery 20230519 1

Oncolytic viruses have recently been proven to be an effective and promising cancer therapeutic strategy, but there is rare data about oncolytic therapy in esophageal squamous cell carcinoma (ESCC), especially oncolytic measles virotherapy. Therefore, this study aimed to explore whether the recombinant measles virus vaccine strain rMV-Hu191 has an oncolytic effect against ESCC cells in vitro and in vivo and elucidate the underlying mechanisms. Our results showed that rMV-Hu191 could efficiently ...[more]

PMID: 37202386

Similar Datasets

Project description:Pyroptosis is a form of programmed cell death, in which gasdermin E (GSDME) plays an important role in cancer cells, which can be induced by activated caspase-3 on apoptotic stimulation. Triclabendazole is a new type of imidazole in fluke resistance and has been approved by the FDA for the treatment of fascioliasis and its functions partially acting through apoptosis-related mechanisms. However, it remains unclear whether triclabendazole has obvious anti-cancer effects on breast cancer cells. In this study, to test the function of triclabendazole on breast cancer, we treated breast cancer cells with triclabendazole and found that triclabendazole induced lytic cell death in MCF-7 and MDA-MB-231, and the dying cells became swollen with evident large bubbles, a typical sign of pyroptosis. Triclabendazole activates apoptosis by regulating the apoptoic protein levels including Bax, Bcl-2, and enhanced cleavage of caspase-8/9/3/7 and PARP. In addition, enhanced cleavage of GSDME was also observed, which indicates the secondary necrosis/pyroptosis is further induced by active caspase-3. Consistent with this, triclabendazole-induced GSDME-N-terminal fragment cleavage and pyroptosis were reduced by caspase-3-specific inhibitor (Ac-DEVD-CHO) treatment. Moreover, triclabendazole induced reactive oxygen species (ROS) elevation and increased JNK phosphorylation and lytic cell death, which could be rescued by the ROS scavenger (NAC), suggesting that triclabendazole-induced GSDME-dependent pyroptosis is related to the ROS/JNK/Bax-mitochondrial apoptotic pathway. Besides, we showed that triclabendazole significantly reduced the tumor volume by promoting the cleavage of caspase-3, PARP, and GSDME in the xenograft model. Altogether, our results revealed that triclabendazole induces GSDME-dependent pyroptosis by caspase-3 activation at least partly through augmenting the ROS/JNK/Bax-mitochondrial apoptotic pathway, providing insights into this on-the-market drug in its potential new application in cancer treatment.

Project description:Histone deacetylase 11 (HDAC11), a sole member of the class IV HDAC subfamily, participates in various cardiovascular diseases. Recent evidence showed that pyroptosis was a form of inflammatory programmed cell death and is critical for atherosclerosis (AS). However, little is known about the effect of HDAC11 on endothelial cell pyroptosis in AS. Thus, this study aims to investigate the role of HDAC11 in vascular endothelial cell pyroptosis and its molecular mechanism. Firstly, we found that HDAC11 expression was up-regulated and pyroptosis occurred in the aorta of ApoE-/- mice fed with a high-fat diet (HFD) for 8 or 12 weeks. Then, in vitro study found the treatment of human umbilical vein endothelial cells (HUVECs) with tumor necrosis factor-α (TNF-α) resulted in pyroptosis, as evidenced by activation of caspase-1 and caspase-3 activation, cleavage of downstream gasdermin D (GSDMD) and gasdermin E (GSDME/DFNA5), the release of pro-inflammatory cytokines interleukin (IL)-1β, IL-6 and IL-18, as well as elevation of LDH activity and increase of propidium iodide (PI)-positive cells. Besides, TNF-α increased HDAC11 expression and induced pyroptosis via TNFR1 in HUVECs. HDAC11 knockdown mitigated pyroptosis by suppressing both NLRP3/caspase-1/GSDMD and caspase-3/GSDME pathways in TNF-α-induced HUVECs. Moreover, GSDME knockdown by siRNA significantly decreased pyroptosis and inflammatory response, while treatment with disulfiram or necrosulfonamide (NSA) further augmented the inhibitory effects of GSDME siRNA on pyroptosis and inflammatory response. Further studies found HDAC11 formed a complex with ERG and decreased the acetylation levels of ERG. More importantly, ERG knockdown augmented vascular endothelial cell pyroptosis in TNF-α-induced HUVECs. Taken together, our study suggests that HDAC11 might promote both NLRP3/caspase-1/GSDMD and caspase-3/GSDME pathways leading to pyroptosis via regulation of ERG acetylation in HUVECs. Modulation of HDAC11 may serve as a potential target for therapeutic strategies of AS.

Dataset Information

Recombinant measles virus vaccine rMV-Hu191 exerts an oncolytic effect on esophageal squamous cell carcinoma via caspase-3/GSDME-mediated pyroptosis.

Publications

Recombinant measles virus vaccine rMV-Hu191 exerts an oncolytic effect on esophageal squamous cell carcinoma via caspase-3/GSDME-mediated pyroptosis.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets