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Host-defence peptide caerin 1.1 and 1.9 inhibited the proliferation of glioblastoma cells

ABSTRACT: Glioblastoma, the most aggressive form of brain cancer, remains a significant global contributor to mortality. Predictions of its increasing incidence in the coming decades underscore the need for more effective treatment strategies. Caerin 1.1 and 1.9, host defence peptides originally isolated from the skin secretions of an Australian tree frog, have exhibited tumour growth inhibition against a diverse spectrum of tumours in vitro. In this study, we reaffirm their potential by demonstrating their inhibitory impact on glioblastoma growth through CCK8 assays. Furthermore, caerin 1.1 and 1.9 effectively curtailed the migration of all tested glioblastoma cells in a cell scratch assay.Quantitative proteomic analysis was employed to investigate the molecular mechanism underlying the anti-proliferative activity.

INSTRUMENT(S): Q Exactive HF

ORGANISM(S): Homo Sapiens (human)

DISEASE(S): Brain Glioblastoma Multiforme

SUBMITTER: Tianfang Wang

LAB HEAD: Tianfang Wang

PROVIDER: PXD044941 | Pride | 2024-06-08

REPOSITORIES: Pride

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			Action	DRS
	Swissprot_Homo_sapiens_20405_20230103.fasta	Fasta
	YAS202210310015_1_F.msf	Msf
	YAS202210310015_1_F1.raw	Raw
	YAS202210310015_1_F10.raw	Raw
	YAS202210310015_1_F2.raw	Raw

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Proteomic analysis of anti-MRSA activity of caerin 1.1/1.9 in a murine skin infection model

Project description:Caerin 1 is a family of host-defense peptides with antimicrobial property originally isolated from Australia tree frog. Caerin 1.1+1.9 has been shown to inhibit multiple antibiotic resistant bacteria infection both in vitro and in vivo. In current study, we compare the MICs of caerin 1.1/1.9 with commonly used antibiotics against S. aureus, Copper-Green Pseudomonas aeruginosa, Acinetobacter baumannii, and Streptococcus haemolyticus. We demonstrate that caerin 1.1/1.9 not only prevent the formation of biofilm by A. Baumann, but also have therapeutic effect on established biofilm. In addition, we find that caerin1.1/1.9 significantly inhibit the growth of methicillin-resistant Staphylococcus aureus (MRSA) strain in a murine skin infection model. The quantitative proteomic analysis suggested that caerin1.1/1.9 largely activate oxidative phosphorylation, as well as several pathways associated with tissue repair and growth, with respect to the untreated tissues infected with MRSA in mice. In summary, our results suggest that caerin 1.1/1.9 have the potential to be used as a drug candidate treating complicated antibiotic resistant bacterial infection in human.

2023-10-11 | PXD044425 | Pride

Intra-tumoral injection of caerin 1.1 and 1.9 peptides in vaccinated TC-1 tumour bearing mice with PD-1 blockade

Project description:Development of a vaccine formula that alters the tumour-infiltrating lymphocytes to be more immune active against a tumour is key to the improvement of clinical responses to immunotherapy. Here, we demonstrate that, in conjunction with E7 antigen specific immunotherapy, and IL-10 and PD-1 blockade, intra-tumoral administration of caerin 1.1 and 1.9 peptides further improves the tumour microenvironment (TME) when compared with injection of a control peptide. We used single cell transcriptomics and mass spectrometry-based proteomics to quantify changes in cellular activity across different cell types within the TME. We show that the injection of caerin 1.1/1.9 increases immune activating macrophages and NK cells, while reducing immunosuppressive macrophages with M2 phenotype, and increased numbers of activated CD8+ T cells with higher populations of memory and effector-memory CD8+ T subsets. Proteomic profiling demonstrated activation of Stat1 modulated apoptosis and production of nitric oxide. Further, computational integration of the proteome with the single cell transcriptome was consistent with deactivation of immune suppressive B cell function following caerin 1.1 and 1.9 treatment.

2021-08-18 | PXD021264 | Pride

Topical application of temperature sensitive gel containing caerin 1.1 and 1.9 peptides on TC-1 tumour bearing mice modulates heterogeneity of macrophage and dendritic cell in the tumour microenvironment

Project description:In this study, we demonstrate that, the topical application of a temperature-sensitive gel containing caerin 1.1 and 1.9 peptides significantly reduces the tumour weight of HPV 16 E6/E7 transformed TC-1 tumour bearing mice via improving the tumour microenvironment (TME) when compared with untreated tumour or a control peptide-containing gel. We use single cell transcriptomics and TMT10 plex-labelling proteomics to quantify changes in cellular activity across different cell types within the TME. We show that caerin 1.1/1.9 gel increased immune activating macrophages, modulated the heterogeneity of NK and dendritic cells to be more pro-inflammatory, and increased numbers of activated CD8+ T cells. Proteomic profiling demonstrated higher innate immune responses, especially the positive regulations of interferon-alpha/beta secretion and response to cytokine stimulus in the caerin gel groups. Further, computational integration of the proteome with the single cell transcriptome consistently suggested more activated T cells and NK cells with the treatment of caerin peptide gel.

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Host-defence peptides caerin 1.1 and 1.9 stimulate TNF-alpha-dependent apoptosis in human cervical cancer HeLa cells

Project description:TNFα pathway has been recognised as one of the most important signalling pathways characterising molecules with anti-cancer activity, due to it closely relates to cell survival as well as apoptosis. Isolated from the glandular secretion of Australian tree frogs, the genus Litoria, host-defence caerin peptides have been previously shown to have multiple biological activities, including anti-proliferation of several cancer cell lines, though the mechanism remains unclear. In this study, we used multiple immunoassays, confocal microscopy in conjunction with TMT-labelling quantitative proteomics to investigate the anti-proliferative activities of caerin 1.1 and 1.9 against cervical cancer HeLa cells. The proteins of cells and cell growth environment post the treatments were comparatively analysed, respectively. We found that both caerin 1.1 and 1.9 highly inhibited HeLa cell proliferation with a significant additive effect. The PPI analysis confirmed that the interactions among the significantly regulated proteins were highly intensive. Besides translation, folding and localisation of proteins and RNA processing, apoptosis process was significantly enriched post the treatments. The apoptosis process was resulted by TNFα signalling, confirmed by the elevated levels of CASP3 and CASP9. Moreover, EGFR1 and androgen receptor pathways appeared inhibited. The activation of TCR pathway derived from the quantitation results further implies the likelihood of recruiting more T cells to the cell growth environment post the treatment and more sensitive to T cell mediated killing of Hela cells.

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Gene profiling: U87 IRE1 dominant negative cells vs. U87ctrl cells in culture

Project description:Transcriptome analysis was performed from human U87 glioblastoma cell clones: U87 IRE1.NCK DN (U87dn, IRE1 dominant negative) and U87 control (U87ctrl, empty plasmid). Cells were grown in DMEM supplemented with 10% FBS and glutamine for 16 hours in culture prior mRNA isolation and analyses U87dn cells expressing a dominant negative transgene of IRE1alpha were compared to U87ctrl cells transfected with the corresponding empty plamid to identify genes associated to tumor invasion and angiogenesis.

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