Benefits and Pitfalls of a Glycosylation Inhibitor Tunicamycin in Therapeutic Implication of Cancers

Published: Jan. 26, 2024

The aberrant glycosylation is a hallmark of cancer progression and chemoresistance. It also an immune therapeutic target for various cancers. Tunicamycin (TM) one the potent nucleo-side antibiotics inhibitor in cells, including breast cancer, gastric pancreatic parallel with inhibition cell growth tumors. Thus, TM can be considered antitumor drug cancers may promote chemosensitivity. Mechanistically, impedes role UDP-HexNAc enzyme biosynthesis oligosaccharides, specialized macromolecules instrumental N-linked glycosylation. Further, like chemotherapies such as doxorubicin (DOX), 5'fluorouracil, etoposide, Cisplatin, induces unfolded protein response (UPR) by blocking Despite TM's effectiveness, its lack cell-type specific cytotoxicity anticancer efficacy. nanoencapsulation techniques materials have been use experiments to reduce improve efficacy targeted therapy. current review profound audit benefits pitfalls cancers, focusing on breast, colon, Additional progressive studies discussed checkpoints other unique pathways. Cytotoxicity possibly adverse effects are highlighted based data from vitro vivo assays. In addition, recent advances nano-based delivery systems regarding emphasized. However, potential this nucleoside re-quires thorough investigation research determine likeliness viable chemotherapeutic.

Language: Английский

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Farnesol Improves Endoplasmic Reticulum Stress and Hepatic Metabolic Dysfunction Induced by Tunicamycin in Mice

Biology, Journal Year: 2025, Volume and Issue: 14(2), P. 213 - 213

Published: Feb. 18, 2025

Endoplasmic reticulum (ER) stress significantly affects liver metabolism, often leading to disorders such as hepatic steatosis. Tunicamycin (TM), a known ER inducer, is frequently used model metabolic stress, but its specific effects on energy homeostasis remain unclear. This study investigates how farnesol (FOH), natural compound with antioxidant and anti-inflammatory properties, counteracts TM-induced associated disruptions in the liver. Using both primary hepatocytes mouse model, this demonstrates that TM treatment caused upregulation of markers, including ATF4, disrupted genes related lipid metabolism gluconeogenesis. Co-treatment FOH reduced these markers restored expression genes. In vivo, alleviated oxidative accumulation, normal glycogen metabolism. Histological analysis further confirmed preserved architecture minimized cellular damage. also stabilized serum profiles modulated key biomarkers, suggesting protective role against injury. These findings suggest has therapeutic potential mitigating stress-related dysfunctions, offering promising insights for diseases linked stress.

Language: Английский

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Computational Modelling of Tunicamycin C Interaction with Potential Protein Targets: Perspectives from Inverse Docking with Molecular Dynamic Simulation

Current Issues in Molecular Biology, Journal Year: 2025, Volume and Issue: 47(5), P. 339 - 339

Published: May 8, 2025

Protein glycosylation plays a crucial role in cancer biology, influencing essential cellular processes such as cell signalling, immune recognition, and tumour metastasis. Therefore, this study highlights the therapeutic potential of targeting treatment, modulating these modifications could disrupt fundamental mechanisms driving progression improve outcomes. Recently, Tunicamycin C, well-known inhibitor, has shown promise breast treatment but remains unexplored colorectal (CRC). Thus, study, we aimed to understand action C CRC using silico studies identify possible drug targets for C. First, identified two target proteins HTDocking algorithm followed by GO KEGG pathway searches: thymidine kinase 1 (TK1) cAMP-dependent protein catalytic subunit alpha (PKAc). Following this, molecular dynamics modelling revealed that binding induced conformational perturbation 3D structures TK1 PKAc, inhibiting their activities. This interaction led stable design, promoting optimal hydrophobic pockets PKAc. Serial validation highlighted active site residues stabilisation. exhibited high affinity with provides way explore repurpose novel inhibitors PKAc new targets, which may block treatment.

Language: Английский

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Glycosylation in cancer: mechanisms, diagnostic markers, and therapeutic applications

Molecular and Cellular Biochemistry, Journal Year: 2025, Volume and Issue: unknown

Published: May 19, 2025

Language: Английский

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Enhancement of Triple-Negative Breast Cancer-Specific Induction of Cell Death by Silver Nanoparticles by Combined Treatment with Proteotoxic Stress Response Inhibitors

Nanomaterials, Journal Year: 2024, Volume and Issue: 14(19), P. 1564 - 1564

Published: Sept. 27, 2024

Metal nanoparticles have been tested for therapeutic and imaging applications in pre-clinical models of cancer, but fears toxicity limited their translation. An emerging concept nanomedicine is to exploit the inherent drug-like properties unmodified nanomaterials cancer therapy. To be useful clinically, there must a window between nanomaterial normal cells. This necessitates identification specific vulnerabilities cancers that can targeted using without inducing off-target toxicity. Previous studies point proteotoxic stress as driver silver nanoparticle (AgNPs) Two key cell responses involved mitigating proteotoxicity are heat shock response (HSR) integrated (ISR). Here, we examine role these play AgNP-induced cytotoxicity triple-negative breast (TNBC) immortalized mammary epithelial Furthermore, investigate HSR ISR inhibitors potential drug partners increase anti-cancer efficacy AgNPs increasing We showed did not strongly induce at transcriptional level, instead decreased expression proteins (HSPs) protein possibly due degradation AgNP-treated TNBC further inhibitor, KRIBB11, synergized with cells, also increased In contrast, found salubrinal, sustain pro-death signaling, enhanced death cells Subsequent co-culture demonstrated combination salubrinal selectively eliminated TNBCs affecting grown same well. Our findings provide additional support mechanism by which kill will help guide future efforts identify would beneficial use

Language: Английский

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Topical Application of Cha-Koji, Green Tea Leaves Fermented with Aspergillus Luchuensis var Kawachii Kitahara, Promotes Acute Cutaneous Wound Healing in Mice

Scientia Pharmaceutica, Journal Year: 2024, Volume and Issue: 92(3), P. 44 - 44

Published: Aug. 12, 2024

“Koji” is one of the most well-known probiotic microorganisms in Japan that contribute to maintenance human health. Although beneficial effects some probiotics on ulcer healing have been demonstrated, there no reports wound koji date. In present study, we investigated “cha-koji”, green tea leaves fermented with Aspergillus luchuensis, cutaneous healing, using a linear incision mouse model. Topical application autoclave-sterilized cha-koji suspension dorsal area healed significantly faster and, notably, less scarring than did or control distilled water treatment. Further vitro experiments revealed accelerated could be attributed its increased anti-bacterial activity, enhanced epidermal cell proliferation and migration, augmented expression anti-inflammatory cytokine transforming growth factor-β1, reduced inflammatory interleukin-6 macrophages, decreased endoplasmic reticulum stress. addition, conducted skin sensitizing potential test, which had adverse posed risk. Thus, may potent therapeutic effect opening up new avenue for clinical as medical aid.

Language: Английский

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