Marine-derived antimicrobial peptide piscidin-1 triggers extrinsic and intrinsic apoptosis in oral squamous cell carcinoma through reactive oxygen species production and inhibits angiogenesis

Free Radical Biology and Medicine, Journal Year: 2024, Volume and Issue: 220, P. 28 - 42

Published: April 27, 2024

Cancer of the head and neck encompasses a wide range cancers, including oral oropharyngeal cancers. Oral cancer is often diagnosed at advanced stages has dismal prognosis. Piscidin-1, marine antimicrobial peptide (AMP) containing approximately 22 amino acids, also exhibits significant anticancer properties. We investigated possible anti-oral effects piscidin-1 clarified mechanisms underlying these effects. treated squamous cell carcinoma lines OC2 SCC4 with Piscidin-1. Cell viability expression different hallmark apoptotic molecules, reactive oxygen species (ROS), were tested using appropriate MTT assay, flow cytometry western blotting assays, human umbilical vein endothelial (HUVEC) wound healing, migration, tube formation (angiogenesis) assays. Piscidin-1 increases cleaved caspase 3 levels to induce apoptosis. ROS intensifies oxidative stress in endoplasmic reticulum mitochondria, causing mitochondrial dysfunction. Additionally, it decreases consumption rates activity complexes I–V. As expected, antioxidants MitoTEMPOL N-acetylcysteine reduce Piscidin-1–induced generation intracellular calcium accumulation. inhibits matrix metalloproteinase (MMP)-2/-9 HUVECs, affecting migration angiogenesis. demonstrated that can promote apoptosis via both intrinsic extrinsic pathways findings indicate anti-proliferative anti-angiogenic properties treatment. Our study on thus provides basis for future translational drug research new theoretical approach clinical research.

Language: Английский

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From defense to offense: antimicrobial peptides as promising therapeutics for cancer

Frontiers in Oncology, Journal Year: 2024, Volume and Issue: 14

Published: Oct. 9, 2024

Antimicrobial peptides (AMPs), naturally occurring components of innate immunity, are emerging as a promising new class anticancer agents. This review explores the potential AMPs novel AMPs, with broad-spectrum antimicrobial activity, exhibit several characteristics that make them attractive candidates for cancer therapy, including selectivity cells, and immunomodulatory effects. Analysis dataset activity reveals their effectiveness is influenced by various structural properties, net charge, length, Boman index, hydrophobicity. These properties contribute to ability target disrupt cell membranes, interfere intracellular processes, modulate immune response. The highlights frontier in treatment, offering hope more effective less toxic therapies. demonstrate therapy through multiple mechanisms, direct cytotoxicity, response modulation, targeting tumor microenvironment, evidenced extensive preclinical studies animal models showing regression, metastasis inhibition, improved survival rates. show significant therapeutics microenvironment targeting, results from early-phase clinical trials. Future research should focus on optimizing AMP developing delivery strategies, exploring synergistic combination therapies fully realize treatments, while addressing challenges related stability, delivery, toxicity.

Language: Английский

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Biological Activity of Peptide Fraction Derived from Hermetia illucens L. (Diptera: Stratiomyidae) Larvae Haemolymph on Gastric Cancer Cells

International Journal of Molecular Sciences, Journal Year: 2025, Volume and Issue: 26(5), P. 1885 - 1885

Published: Feb. 22, 2025

Gastric cancer (GC) is one of the leading causes cancer-related mortality worldwide, characterised by poor prognosis and limited responsiveness to chemotherapy. There a need for new more effective anticancer agents. Antimicrobial peptides (AMPs) represent promising class biomolecules this purpose. Naturally occurring in innate immune system, these can also exert cytotoxic effects against cells, earning them designation "anticancer peptides" (ACPs). They have potential be viable support current chemotherapy schedules due their selectivity cells minor propensity induce chemoresistance cells. Insects are an excellent source AMPs. Among them, its ability thrive hostile microorganism-rich environments, we isolated peptide fraction from Hermetia illucens L. (Diptera: Stratiomyidae) haemolymph evaluate possible activity. We tested Peptide Fractions (PFs) AGS KATO III gastric cell lines. Data obtained indicated that PFs, especially those resulting Escherichia coli Micrococcus flavus infection (to boost response), were able inhibit tumour growth inducing apoptosis or cycle arrest line-specific manner. These results further investigation into use antimicrobial produced insects as

Language: Английский

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Porcine Recombinant NK-Lysin Inhibits the Growth and Metastasis of Murine Hepatocellular Carcinoma In Vivo

Molecules, Journal Year: 2025, Volume and Issue: 30(6), P. 1234 - 1234

Published: March 10, 2025

Porcine recombinant NK-lysin (prNK-lysin) has been shown to inhibit the proliferation and metastasis of hepatocellular carcinoma (HCC) cells in vitro. However, its effects on HCC vivo remain unclear. In this study, an allograft murine model using cell line Hepa1-6 was employed investigate anticancer prNK-lysin. Initially, vitro efficacy prNK-lysin evaluated cells, demonstrating that effectively inhibited both metastasis. These were mediated through induction oncosis suppression Fascin-1, MMP-2, MMP-9 protein expressions. Subsequently, assessed a mouse liver orthotopic implantation lung BALB/cA-nu mice. The administration 13 mg/kg could tumor growth lungs. Our results demonstrate possesses strong anti-HCC vivo, with inhibition expressions as potential molecular mechanisms for activity.

Language: Английский

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Hybrid Anticancer Peptide Synergistically Improving Cancer Cell Uptake and Inducing Apoptosis Mediated by Membrane Fusion

Biomacromolecules, Journal Year: 2025, Volume and Issue: unknown

Published: March 10, 2025

Anticancer peptides (ACPs) have exhibited tremendous potential in tumor treatment. However, low peptide delivery efficiency limits some ACPs' clinical application. Herein, we designed a hybrid named AFP-KLA and investigated the cell-specific targeting ability proapoptotic properties. Our results revealed that AFP primarily facilitated selective binding of KLA to cell membranes, enabling whole enter cells via membrane fusion. Furthermore, demonstrated superior colocalization within MCF-7 induced apoptosis by disrupting mitochondrial membrane. Subsequently, constructed model subcutaneously mice tested antitumor activity ACP vivo. We observed could effectively inhibit growth displayed excellent activity. In summary, these suggest is possibly promising therapeutic agent for targeted therapy breast cancer can guide future design ACPs.

Language: Английский

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Exploring the potential of anticancer peptides as therapeutic agents for cancer treatment

Research in Pharmaceutical Sciences, Journal Year: 2025, Volume and Issue: 20(2), P. 165 - 187

Published: March 1, 2025

Despite great advances in cancer identification and treatment, malignancies remain the primary cause of high morbidity mortality worldwide. The drawbacks conventional chemotherapy, such as severe toxicity, lack specificity related to actively dividing cells, resistance, can warrant urgent need develop an alternative approach treat this disease. To overcome drawbacks, researchers are attempting deliver drugs site action (targeted delivery) or identify that specifically target tumor cells. In regard, highly cationic amphipathic antimicrobial peptides attracting attention due their potent anticancer activity, low cost manufacture, and, most critically, tumor-targeting activity. A growing number documents have shown some mentioned exhibited a broad spectrum cytotoxic activity against cells but not normal mammalian entitled peptides. Due solubility, strong penetration, selectivity, ability be used alone conjunction with other medications, potential become very successful treatments future. This review provided overview studies concerning peptide classification, modes action, also summarized developed for targeting different types malignancies. role silico methods artificial intelligence design discovery was briefly explained. Additionally, current addressed challenges utilizing therapy highlighted currently undergoing clinical trials.

Language: Английский

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D-M159 Synergistically Induces Apoptosis in HeLa Cells Through Endoplasmic Reticulum Stress and Mitochondrial Dysfunction

International Journal of Molecular Sciences, Journal Year: 2025, Volume and Issue: 26(7), P. 3172 - 3172

Published: March 29, 2025

Pore-forming peptides are promising antimicrobial and anticancer agents due to their membrane selectivity biodegradability. Our prior work identified peptide M159, which permeabilized synthetic phosphatidylcholine liposomes without mammalian cell toxicity. Here, we report that the D-type variant (D-M159) induces apoptosis in HeLa cells under starvation. To explore its mechanism, analyzed D-M159 cytotoxicity, intracellular uptake, apoptotic pathways via flow cytometry, confocal microscopy, Western blot. Calcium dynamics mitochondrial function were examined specific labeling functional assays. Results revealed exhibited starvation-dependent, dose-responsive cytotoxicity triggered cells. Mechanistic studies indicated entered caveolin-dependent caveolae-dependent endocytosis induced endoplasmic reticulum stress by up-regulating proteins such as ATF6, p-IRE1, PERK, GRP78, CHOP. Meanwhile, promoted expression of IP3R1, GRP75, VDAC1, led calcium iron overload, decreased potential, increased reactive oxygen species (ROS) generation, thereby activating pathway inducing aberrant Bax, Bcl-2, Caspase-9, Caspase-3. This study showed synergistically starved through dysfunction, demonstrating potential a novel agent.

Language: Английский

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Emerging therapies for osteoporosis: a narrative review of multifaceted interventions involving plant- and animal-derived bioactive peptides

Aging advances., Journal Year: 2025, Volume and Issue: 2(2), P. 54 - 61

Published: April 8, 2025

Osteoporosis is a chronic bone disease associated with aging, characterized by decreased mineral density and increased fracture risk, profoundly impacting the quality of life older individuals. Despite significant advancements in modern medicine, existing treatments for osteoporosis are often accompanied substantial side effects that limit their long-term use. In recent years, use plant-derived animal-derived bioactive peptides has emerged as promising due to high safety profile, low effects, natural health benefits. This review aims explore pathogenesis osteoporosis, extraction, isolation, purification peptides, antiosteoporotic mechanisms. Additionally, this seeks provide safer more effective solutions prevention treatment The plant- mediated through multiple mechanisms, including promotion osteoblast proliferation differentiation, inhibition osteoclast activity, modulation calcium phosphorus metabolism, reduction oxidative stress, suppression inflammatory responses. For example, certain promote formation activating Wnt/β-catenin signaling pathway, while others reduce resorption inhibiting RANKL/RANK/OPG axis. addition, some enhance regulating absorption exerting antioxidant functions. However, currently, there insufficient clinical evidence application require further validation trials. Plant- hold potential an emerging antiosteoporosis strategy, particularly among With continued research into mechanisms action advancement trials, these anticipated become important tools improving reducing risk population. Future studies should develop programs.

Language: Английский

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A new short pH-responsive anticancer peptide derived by intramolecular charge shielding strategy

European Journal of Medicinal Chemistry, Journal Year: 2025, Volume and Issue: 291, P. 117662 - 117662

Published: April 19, 2025

Language: Английский

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Progress in the classification, optimization, activity, and application of antimicrobial peptides

Frontiers in Microbiology, Journal Year: 2025, Volume and Issue: 16

Published: April 23, 2025

Antimicrobial peptides (AMPs) come from various sources and exhibit unique antimicrobial properties. Their rapid action, effectiveness, resistance to development make them promising alternatives combat antibiotic resistance. In addition its excellent antibacterial properties, AMPs have superior immunomodulatory, antitumor, antiviral activities. recent years, the demand for has continued increase in many fields, especially medical field, prospects are extensive. However, disadvantages of expensive cost, higher hemolysis, short half-life, susceptibility degradation by protein hydrolases, low bioavailability, toxic side effects, other disadvantages, which seriously limit wide application AMPs. Therefore, fewer been approved marketing or undergoing clinical trials. The review covers period 2001 2025 provides a detailed discussion searching databases such as Google Scholar Web Science. This paper reviews progress research on sources, structures, optimization strategies, biological activities, mechanisms applications. general, approaches number new increased significantly. improvement technologies high poor stability, bioavailability cost is still high, but widely used clinical, food, livestock, poultry, cosmetics fields. article focuses commonly strategies main activities AMPs, aiming effectively respond challenges provide theoretical basis expanding their range.

Language: Английский

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