Lentinan-functionalized Selenium Nanoparticles target Tumor Cell Mitochondria via TLR4/TRAF3/MFN1 pathway
| Autor: | Man-Xi Lu, Piao-Piao Liu, Yang Zhang, Honggang Zhou, Zihan Zhao, Yuan Qin, Bo Sun, Fang Cui, Huijuan Liu, Denghui Zhai, Ce Luo, Kun Li, Shuang Chen, Heng-Wei Xu, Jia-Huan Yang, Tao Sun, Cheng Yang |
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| Rok vydání: | 2020 |
| Předmět: |
Proteomics
Lentinan Medicine (miscellaneous) Antineoplastic Agents Apoptosis Mitochondrion Caveolae Endocytosis Mitochondrial Membrane Transport Proteins GTP Phosphohydrolases mitochondria targeting pathway Mice Selenium 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine lentinan Cell Line Tumor selenium nanoparticles Animals Humans Pharmacology Toxicology and Pharmaceutics (miscellaneous) 030304 developmental biology Membrane Potential Mitochondrial Ovarian Neoplasms Mice Inbred BALB C 0303 health sciences TNF Receptor-Associated Factor 3 Mitochondrial membrane fusion malignant ascites Mitochondria Toll-Like Receptor 4 ovarian cancer Endocytic vesicle chemistry 030220 oncology & carcinogenesis Caveolin 1 Cancer cell Cancer research Nanoparticles Female Reactive Oxygen Species Signal Transduction Research Paper |
| Zdroj: | Theranostics |
| ISSN: | 1838-7640 |
| Popis: | Rationale: Malignant ascites caused by cancer cells results in poor prognosis and short average survival time. No effective treatment is currently available for malignant ascites. In this study, the effects of lentinan (LNT)-functionalized selenium nanoparticles (Selene) on malignant ascites were evaluated. Furthermore, the mechanism of Selene targeting mitochondria of tumor cells were also investigated. Methods: Selene were synthesized and characterized by TEM, AFM and particle size analysis. The OVCAR-3 and EAC cells induced ascites models were used to evaluate the effects of Selene on malignant ascites. Proteomic analysis, immunofluorescence, TEM and ICP-MS were used to determine the location of Selene in tumor cells. Mitochondrial membrane potential, ROS, ATP content, and caspase-1/3 activity were detected to evaluate the effect of Selene on mitochondrial function and cell apoptosis. Immunofluorescence, Co-IP, pull-down, duolink, Western blot, and FPLC were used to investigate the pathway of Selene targeting mitochondria. Results: Selene could effectively inhibit ascites induced by OVCAR-3 and EAC cells. Selene was mainly located in the mitochondria of tumor cells and induced apoptosis of tumor cells. The LNT in Selene was involved in caveolae-mediated endocytosis through the interaction between toll-like receptor-4 (TLR4) and caveolin 1 (CAV1). Furthermore, the Selene in the endocytic vesicles could enter the mitochondria via the mitochondrial membrane fusion pathway, which was mediated by TLR4/TNF receptor associated factor 3 (TRAF3)/mitofusin-1 (MFN1) protein complex. Conclusion: Selene is a candidate anticancer drug for the treatment of malignant ascites. And TLR4/TRAF3/MFN1 may be a specific nano-drug delivery pathway that could target the mitochondria. |
| Databáze: | OpenAIRE |
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