Objective: To test cell penetrating and interfering peptide Mut3DPT-PP2A/SET in interaction between serine threonine phosphatase PP2A and its physiological inhibitor, the oncoprotein SET.
Materials And Methods: Adult male C3H/S-strain mice, 60 days old, were given a graft of breast adenocarcinoma cells (TN60) into subcutaneous tissue. Mut3DPT-PP2A/SET peptide was used to block PP2A and SET oncoprotein interaction. The graft-bearing animals were divided into a control group (injected with saline buffer), and an intervention group injected intraperitoneally with Mut3DPT-PP2A/SET peptide (5 mg/kg) every day from day 5 to day 37. The variables we used to compare the outcome in both groups were tumor size in mm (length×width) and histological changes. In the statistical analysis we used ANOVA and Student-Keuls multiple comparisons test and Tuckey for the post-test analysis.
Results: 48 mice were grafted at day 0 with breast UNLP-C3H/S tumor cells, and after randomization, they were assigned to one of the two study groups. At day 5 all mice were injected either with placebo or with the peptide. The treated group showed significant tumor reduction (p<0.07). Histological changes showed presence of apoptosis and necrosis of tumor in treated group.
Conclusion: The peptide Mut3DPT-PP2A/SET has demonstrated anti-tumor activity by reduction in vivo of tumor growth becoming a promising future in anticancer therapy.
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http://dx.doi.org/10.3897/folmed.62.e47737 | DOI Listing |
Peptides play critical roles in cellular functions such as signaling and immune regulation, and peptide-based biotherapeutics show great promise for treating various diseases. Among these, cell-penetrating peptides (CPPs) are particularly valuable for drug delivery due to their ability to cross cell membranes. However, the mechanisms underlying CPP-mediated transport, especially across the blood-brain barrier (BBB), remain poorly understood.
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February 2025
Department of Biochemistry and Molecular Pharmacology. Istituto di Ricerche Farmacologiche Mario Negri, IRCCS, Via Mario Negri, 2, Milan, Italy.
Targeting is the most challenging problem to solve for drug delivery systems. Despite the use of targeting units such as antibodies, peptides and proteins to increase their penetration in tumors the amount of therapeutics that reach the target is very small, even with the use of nanoparticles (NPs). Nature has solved the selectivity problem using a combination of proteins and lipids that are exposed on the cell membranes and are able to recognize specific tissues as demonstrated by cancer metastasis.
View Article and Find Full Text PDFACS Cent Sci
January 2025
Centre for Inflammation Research, The University of Edinburgh, EH16 4UU Edinburgh, U.K.
The cellular uptake routes of peptides and proteins are complex and diverse, often handicapping therapeutic success. Understanding their mechanisms of internalization requires chemical derivatization with approaches that are compatible with wash-free and real-time imaging. In this work, we developed a new late-stage labeling strategy for unprotected peptides and proteins, which retains their biological activity while enabling live-cell imaging of uptake and intracellular trafficking.
View Article and Find Full Text PDFAdv Mater
January 2025
Department of Physics, Tsinghua University, Beijing, 100084, China.
Lithium dendrite penetration through solid electrolyte has been the major obstacle for practical sulfide-based all-solid-state lithium metal batteries (ASSLMBs). Herein, a series of tailored model solid cells are designed to investigate the intrinsic lithium growth behavior at open surfaces and internal cracks of sulfide solid electrolyte. It is shown that when plating lithium on the open surface of electrolyte (free space), the lithium exhibits an intrinsic columnar growth behavior perpendicular to the electrolyte surface, preferentially along the (110) crystal axis.
View Article and Find Full Text PDFBiochemistry (Mosc)
December 2024
Institute of Cytology and Genetics, Siberian Branch of the Russian Academy of Sciences, Novosibirsk, 630090, Russia.
The auxin-inducible degron (AID) system is widely used to study function of various proteins. The plant hormone auxin is used as an inducer in this system, which easily penetrates into the cells and causes proteasomal degradation of the protein of interest fused to a small degron tag. It is often assumed that as a plant hormone, auxin does not significantly affect physiology of animal cells.
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