Therapeutic effects of antimicrobial peptide on malignant ascites in a mouse model

Li, Xia; Wu, Yanling; Ma, Junsheng; Zhang, Fuchun

doi:10.3892/mmr.2018.8691

Cited by 7 publications

(6 citation statements)

References 21 publications

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“…This selective antitumor activity might in part depend on the variable membrane compositions and fluidity of transformed compared to non-transformed cells [122]. Finally, Cec antitumor activity was also demonstrated in in vivo mammalian models, as shown for the H. cecropia Cec B and B. mori -derived Cec XJ, both improving the survival of mice bearing malignant ascites [117,123], indicating the potential of these AMPs as anticancer therapeutics.…”

Section: Antitumor Activity Of Natural Cecs and Synthetic Cec-analogsmentioning

confidence: 99%

Insect Cecropins, Antimicrobial Peptides with Potential Therapeutic Applications

Brady

Grapputo

Romoli

et al. 2019

IJMS

136

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The alarming escalation of infectious diseases resistant to conventional antibiotics requires urgent global actions, including the development of new therapeutics. Antimicrobial peptides (AMPs) represent potential alternatives in the treatment of multi-drug resistant (MDR) infections. Here, we focus on Cecropins (Cecs), a group of naturally occurring AMPs in insects, and on synthetic Cec-analogs. We describe their action mechanisms and antimicrobial activity against MDR bacteria and other pathogens. We report several data suggesting that Cec and Cec-analog peptides are promising antibacterial therapeutic candidates, including their low toxicity against mammalian cells, and anti-inflammatory activity. We highlight limitations linked to the use of peptides as therapeutics and discuss methods overcoming these constraints, particularly regarding the introduction of nanotechnologies. New formulations based on natural Cecs would allow the development of drugs active against Gram-negative bacteria, and those based on Cec-analogs would give rise to therapeutics effective against both Gram-positive and Gram-negative pathogens. Cecs and Cec-analogs might be also employed to coat biomaterials for medical devices as an approach to prevent biomaterial-associated infections. The cost of large-scale production is discussed in comparison with the economic and social burden resulting from the progressive diffusion of MDR infectious diseases.

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Section: Antitumor Activity Of Natural Cecs and Synthetic Cec-analogsmentioning

confidence: 99%

Insect Cecropins, Antimicrobial Peptides with Potential Therapeutic Applications

Brady

Grapputo

Romoli

et al. 2019

IJMS

136

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“…CXJ is a cationic AMP isolated from larvae of Bombyx mori belonging to the cecropin-B family. Most importantly, it is one of the few peptides with activity against EC [ 4 ] and also targets other cancer types such as gastric [ 4 , 5 , 39 ] or hepatocellular carcinoma [ 6 ]. Despite its potent anticancer activity, its mechanism of action is unknown, although it does not seem to affect the plasma membrane, suggesting that its action relies on other mechanisms [ 5 ].…”

Section: Introductionmentioning

confidence: 99%

Molecular Basis of the Anticancer and Antibacterial Properties of CecropinXJ Peptide: An In Silico Study

Ramos‐Martín

D’Amelio

2021

IJMS

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Esophageal cancer is an aggressive lethal malignancy causing thousands of deaths every year. While current treatments have poor outcomes, cecropinXJ (CXJ) is one of the very few peptides with demonstrated in vivo activity. The great interest in CXJ stems from its low toxicity and additional activity against most ESKAPE bacteria and fungi. Here, we present the first study of its mechanism of action based on molecular dynamics (MD) simulations and sequence-property alignment. Although unstructured in solution, predictions highlight the presence of two helices separated by a flexible hinge containing P24 and stabilized by the interaction of W2 with target biomembranes: an amphipathic helix-I and a poorly structured helix-II. Both MD and sequence-property alignment point to the important role of helix I in both the activity and the interaction with biomembranes. MD reveals that CXJ interacts mainly with phosphatidylserine (PS) but also with phosphatidylethanolamine (PE) headgroups, both found in the outer leaflet of cancer cells, while salt bridges with phosphate moieties are prevalent in bacterial biomimetic membranes composed of PE, phosphatidylglycerol (PG) and cardiolipin (CL). The antibacterial activity of CXJ might also explain its interaction with mitochondria, whose phospholipid composition recalls that of bacteria and its capability to induce apoptosis in cancer cells.

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“…Body weight was the direct index for determining the development of abdominal ascites tumors in mice [ 40 ]. To determine the effect of MS275 on malignant ascites formation and tumor growth, mice were administered with MS275 every other day for 4 consecutive intraperitoneal injection since the ascites models are formed.…”

Section: Resultsmentioning

confidence: 99%

MS275 as Class I HDAC inhibitor displayed therapeutic potential on malignant ascites by iTRAQ-based quantitative proteomic analysis

Wang

Wei

et al. 2022

BMC Gastroenterol

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Background Malignant ascites is a manifestation of end stage events in a variety of cancers and is associated with significant morbidity. Epigenetic modulators play a key role in cancer initiation and progression, among which histone deacetylases (HDACs) are considered as one of the most important regulators for various cancer development, such as liver cancer, ovarian cancer, and pancreatic cancer et al. Thus, in this paper, we sought to explore the therapeutic effect of HDAC inhibitor on malignant ascites. Methods In this report, we tested the therapeutic effect of different isoform selective HDAC inhibitors (Class I HDACI MS275, Class IIa HDACI MC1568, pan-HDAC inhibitors SAHA) on malignant ascites in vitro and in vivo. We further used proteome analysis to find the potential mechanisms for malignant ascites therapy. Results Among the different isoform-selective HDAC inhibitors, the class I selective HDACI, MS275, exhibited preferential inhibition on various ascites cells. MS275 could induce cell cycle arrest in G0/G1 phase and promote apoptosis on ascites cells. Through proteome analysis, we found MS275 could downregulate proteins related to cell cycle progression, such as CDK4, CDC20, CCND1; MS275 could upregulate pro-apoptosis proteins such as PAPR1, LMNB2 and AIFM1; in addition, MS275 could change the expression of tumorigenic proteins related to the specific malignant ascites bearing tumors, such as TSP1 and CDK4 for bladder cancer. We then confirmed that abemaciclib (CDK4/6 selective inhibitor) could inhibit the proliferation of ascites cells, and the combination of abemaciclib and MS275 had synergistic anti-tumor effect. Finally, we found that MS275 could in vivo inhibit malignant ascites progression (ascites volume: 2.9 ± 1.0 mL vs 7.5 ± 1.2 mL, p < 0.01), tumor growth, and prolong 66% of the life-span when compared with the untreated group. Conclusion This present research revealed that the class I selective HDAC inhibitor, MS275, could effectively inhibit malignant ascites development and tumor growth via multiple pathways. These results indicated that HDACI could have great potential for clinical therapy of malignant ascites.

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Therapeutic effects of antimicrobial peptide on malignant ascites in a mouse model

Cited by 7 publications

References 21 publications

Insect Cecropins, Antimicrobial Peptides with Potential Therapeutic Applications

Insect Cecropins, Antimicrobial Peptides with Potential Therapeutic Applications

Molecular Basis of the Anticancer and Antibacterial Properties of CecropinXJ Peptide: An In Silico Study

MS275 as Class I HDAC inhibitor displayed therapeutic potential on malignant ascites by iTRAQ-based quantitative proteomic analysis

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