Prostate apoptosis response-4 (PAR-4) is considered as a tumour suppressor due to its ability to selectively induce cell apoptosis in most cancer cells. However little is known about the role of PAR-4 in ovarian cancer. In this study, we investigated for the first time the role of PAR-4 in ovarian carcinogenesis. We showed that PAR-4 mRNA level is not significantly different between healthy and cancer ovarian cells. Immunohistochemistry on ovarian tissue showed that ovarian cancer cells are positive for PAR-4 nuclear and cytoplasmic staining whereas ovarian healthy cells are negative for PAR-4 nuclear staining. We then studied the role of PAR-4 in cell apoptosis. We determined that PAR-4 induces cell apoptosis in response to stimuli, in vitro, but is also involved in the relocation of GRP78 from endoplasmic reticulum to the cell surface of ovarian cancer cell line (SKOV-3 cells). In ovo, PAR-4 decreases ovarian tumour development and increases the response to taxol treatment. These observations suggest that PAR-4 is a very interesting therapeutic target against ovarian carcinogenesis.
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http://dx.doi.org/10.18632/oncotarget.4010 | DOI Listing |
Biochimie
January 2025
Laboratory of Applied Toxinology, Center of Toxins, Immune-Response and Cell Signaling (CeTICS), Butantan Institute, São Paulo, Brazil. Electronic address:
PA-BJ is a serine protease present in Bothrops jararaca venom that triggers platelet aggregation and granule secretion by activating the protease-activated receptors PAR-1 and PAR-4, without clotting fibrinogen. These receptors also have a relevant role in endothelial cells, however, the interaction of PA-BJ with other membrane-bound or soluble targets is not known. Here we explored the activity of PA-BJ on endothelial cell receptor, cytoskeleton, and coagulation proteins in vitro, and show the degradation of fibrinogen and protein C, and the limited proteolysis of actin, EPCR, PAR-1, and thrombomodulin.
View Article and Find Full Text PDFBiogerontology
December 2024
Department of Biochemistry, North Eastern Hill University, Shillong, Meghalaya, 793022, India.
Aging represents the gradual accumulation of alterations within an organism over time. The physical and chemical characteristics of our cells gradually change as we age, making it more difficult for our tissues and organs to self-regulate, regenerate, and maintain their structural and functional integrity. AMP- activated protein kinase (AMPK), a well-known sensor of cellular energy status acts as a central regulator of an integrated signalling network that control homeostasis, metabolism, stress resistance, cell survival and autophagy.
View Article and Find Full Text PDFCells
September 2024
Department of Toxicology and Cancer Biology, University of Kentucky, 538 Healthy Kentucky Research Building, 760 Press Avenue, Lexington, KY 40536, USA.
Prostate apoptosis response-4 (Par-4, also known as PAWR) is a ubiquitously expressed tumor suppressor protein that induces apoptosis selectively in cancer cells, while leaving normal cells unaffected. Our previous studies indicated that genetic loss of Par-4 promoted hepatic steatosis, adiposity, and insulin-resistance in chow-fed mice. Moreover, low plasma levels of Par-4 are associated with obesity in human subjects.
View Article and Find Full Text PDFAnn Hepatol
October 2024
Hainan Provincial Key Laboratory of Carcinogenesis and Intervention, Hainan Medical University, Hiakou 571199, Hainan Province, PR China; Department of Medical Oncology, The Second Affiliated Hospital, Hainan Medical University, Haikou 570311,Hainan Province, PR China; Institution of Tumor, Hainan Medical University, Hiakou 570102, Hainan Province, PR China. Electronic address:
Biochem Pharmacol
November 2024
College of Veterinary Medicine, Shanxi Agricultural University, 030801 Taigu, Shanxi, China; Shanxi Key Laboratory of Ecological Animal Science and Environmental Veterinary Medicine, College of Veterinary Medicine, Shanxi Agricultural University, 030801 Taigu, Shanxi, China. Electronic address:
The emerging antibiotic-resistant bacteria, especially the "ESKAPE" pathogens, pose a continuous threat to global health. In this study, we explored metalloantibiotics as promising therapeutics and innovative antimicrobial agents. The role of metal in the antimicrobial activity of chloroxine (5,7-dichloro-8-hydroxyquinoline), as a metalloantibiotic, was investigated by minimal inhibit concentration (MIC) assay and a series of assays, including growth curve, time-killing, and UV-visible spectroscopy and PAR (4-(2-pyridylazo)-resorcinol) competition assays.
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