Ergolide mediates anti-cancer effects on metastatic uveal melanoma cells and modulates their cellular and extracellular vesicle proteomes DOI Creative Commons
Husvinee Sundaramurthi, Valentina Tonelotto, Kieran Wynne

et al.

Open Research Europe, Journal Year: 2023, Volume and Issue: 3, P. 88 - 88

Published: June 8, 2023

Background: Uveal melanoma is a poor prognosis cancer. Ergolide, sesquiterpene lactone isolated from Inula Brittanica, exerts anti-cancer properties. The objective of this study was to 1) evaluate whether ergolide reduced metastatic uveal (MUM) cell survival/viability in vitro and vivo; 2) understand the molecular mechanism action. Methods: Ergolide bioactivity screened via long-term proliferation assay in UM/MUM cells zebrafish MUM xenograft models. Mass spectrometry profiled proteins modulated by within whole or extracellular vesicle (EVs) lysates OMM2.5 line. Protein expression analyzed immunoblots correlation analyses UM patient survival used Cancer Genome Atlas (TCGA) data. Results: Ergolide treatment resulted significant, dose-dependent reductions (48.5 99.9%; p<0.0001) normalized primary fluorescence (56%; vivo, compared vehicle controls. Proteome-profiling ergolide-treated cells, identified 5023 proteins, with 52 55 significantly altered at 4 24 hours, respectively (p<0.05; fold-change >1.2). Immunoblotting heme oxygenase 1 (HMOX1) growth/differentiation factor 15 (GDF15) corroborated proteomic data. Additional proteomics EVs treated ergolide, detected 2931 proteins. There large overlap EV annotated Vesiclepedia compendium. Within differentially expressed proteasomal pathway primarily altered. Interestingly, BRCA2 CDKN1A Interacting (BCCIP) Chitinase Domain Containing (CHID1), were only both cellular isolates they displayed inverse differential versus EVs. Conclusions: novel, promising anti-proliferative agent for UM/MUM. Proteomic profiling cellular/EV candidate pathways elucidating action putative biomarkers UM, that require further examination.

Language: Английский

Epigenetics and Control of Tumor Angiogenesis in Melanoma: An Update with Therapeutic Implications DOI Open Access
Gerardo Cazzato, Nicoletta Sgarro, Nadia Casatta

et al.

Cancers, Journal Year: 2024, Volume and Issue: 16(16), P. 2843 - 2843

Published: Aug. 14, 2024

Angiogenesis, the formation of new blood vessels from pre-existing ones, is a crucial process in progression and metastasis melanoma. Recent research has highlighted significant role epigenetic modifications regulating angiogenesis. This review comprehensively examines current understanding how mechanisms, including DNA methylation, histone modifications, non-coding RNAs, influence angiogenic pathways key modification, can silence angiogenesis inhibitors such as thrombospondin-1 TIMP3 while promoting pro-angiogenic factors like vascular endothelial growth factor (VEGF). Histone methylation acetylation, also play pivotal expression angiogenesis-related genes. For instance, acetylation histones H3 H4 associated with upregulation genes, whereas patterns either enhance or repress signals, depending on specific mark context. Non-coding particularly microRNAs (miRNAs) further modulate miRNAs, miR-210, have been identified regulators, miR-9 by targeting E-cadherin enhancing VEGF. discusses therapeutic potential to inhibit Epigenetic drugs, methyltransferase (e.g., 5-azacytidine) deacetylase Vorinostat), shown promise preclinical models reactivating downregulating factors. Moreover, modulation miRNAs lncRNAs presents novel approach for anti-angiogenic therapy.

Language: Английский

Citations

4
Design, Synthesis, and Biological Evaluation of Novel Quinazolin-4(3H)-one-Based Histone Deacetylase 6 (HDAC6) Inhibitors for Anticancer Activity DOI Open Access
Yogesh Mahadu Khetmalis, Ashna Fathima,

Markus Schweipert

et al.

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(13), P. 11044 - 11044

Published: July 3, 2023

A series of novel quinazoline-4-(3H)-one derivatives were designed and synthesized as histone deacetylase 6 (HDAC6) inhibitors based on the cap group benzhydroxamic acid linker metal-binding group. total 19 analogues (5a-5s) obtained. The structures target compounds characterized using 1H-NMR, 13C-NMR, LC-MS, elemental analyses. Characterized screened for inhibition against HDAC8 class I, HDAC4 IIa, HDAC6 IIb. Among tested, 5b proved to be most potent selective inhibitor with an IC50 value 150 nM. Some these showed antiproliferative activity in several tumor cell lines (HCT116, MCF7, B16). Amongst all tested their anticancer effect cancer lines, 5c emerged active MCF-7 line 13.7 μM; it exhibited cell-cycle arrest G2 phase, well promoted apoptosis. Additionally, we noted a significant reduction colony-forming capability cells presence 5c. At intracellular level, was enumerated by monitoring acetylation α-tubulin limited acetyl-H3. Importantly, obtained results suggested at sub-micromolar concentrations compared other molecules vitro.

Language: Английский

Citations

9
Ergolide mediates anti-cancer effects on metastatic uveal melanoma cells and modulates their cellular and extracellular vesicle proteomes DOI Creative Commons
Husvinee Sundaramurthi, Valentina Tonelotto, Kieran Wynne

et al.

Open Research Europe, Journal Year: 2023, Volume and Issue: 3, P. 88 - 88

Published: Nov. 13, 2023

Background Uveal melanoma is a poor prognosis cancer. Ergolide, sesquiterpene lactone isolated from Inula Brittanica, exerts anti-cancer properties. The objective of this study was to 1) evaluate whether ergolide reduced metastatic uveal (MUM) cell survival/viability in vitro and vivo; 2) understand the molecular mechanism action. Methods Ergolide bioactivity screened via long-term proliferation assay in UM/MUM cells zebrafish MUM xenograft models. Mass spectrometry profiled proteins modulated by within whole or extracellular vesicle (EVs) lysates OMM2.5 line. Protein expression analyzed immunoblots correlation analyses UM patient survival used Cancer Genome Atlas (TCGA) data. Results treatment resulted significant, dose-dependent reductions (48.5 99.9%; p<0.0001) normalized primary fluorescence (56%; vivo, compared vehicle controls. Proteome-profiling ergolide-treated cells, identified 5023 proteins, with 52 55 significantly altered at 4 24 hours, respectively (p<0.05; fold-change >1.2). Immunoblotting heme oxygenase 1 (HMOX1) growth/differentiation factor 15 (GDF15) corroborated proteomic Additional proteomics EVs treated ergolide, detected 2931 proteins. There large overlap EV annotated Vesiclepedia compendium. Within differentially expressed proteasomal pathway primarily altered. Interestingly, BRCA2 CDKN1A Interacting (BCCIP) Chitinase Domain Containing (CHID1), were only both cellular isolates they displayed inverse differential versus EVs. Conclusions novel, promising anti-proliferative agent for UM/MUM. Proteomic profiling cellular/EV candidate pathways elucidating action putative biomarkers UM, that require further examination.

Language: Английский

Citations

5
Ergolide mediates anti-cancer effects on metastatic uveal melanoma cells and modulates their cellular and extracellular vesicle proteomes DOI Creative Commons
Husvinee Sundaramurthi, Valentina Tonelotto, Kieran Wynne

et al.

Open Research Europe, Journal Year: 2023, Volume and Issue: 3, P. 88 - 88

Published: June 8, 2023

Background: Uveal melanoma is a poor prognosis cancer. Ergolide, sesquiterpene lactone isolated from Inula Brittanica, exerts anti-cancer properties. The objective of this study was to 1) evaluate whether ergolide reduced metastatic uveal (MUM) cell survival/viability in vitro and vivo; 2) understand the molecular mechanism action. Methods: Ergolide bioactivity screened via long-term proliferation assay in UM/MUM cells zebrafish MUM xenograft models. Mass spectrometry profiled proteins modulated by within whole or extracellular vesicle (EVs) lysates OMM2.5 line. Protein expression analyzed immunoblots correlation analyses UM patient survival used Cancer Genome Atlas (TCGA) data. Results: Ergolide treatment resulted significant, dose-dependent reductions (48.5 99.9%; p<0.0001) normalized primary fluorescence (56%; vivo, compared vehicle controls. Proteome-profiling ergolide-treated cells, identified 5023 proteins, with 52 55 significantly altered at 4 24 hours, respectively (p<0.05; fold-change >1.2). Immunoblotting heme oxygenase 1 (HMOX1) growth/differentiation factor 15 (GDF15) corroborated proteomic data. Additional proteomics EVs treated ergolide, detected 2931 proteins. There large overlap EV annotated Vesiclepedia compendium. Within differentially expressed proteasomal pathway primarily altered. Interestingly, BRCA2 CDKN1A Interacting (BCCIP) Chitinase Domain Containing (CHID1), were only both cellular isolates they displayed inverse differential versus EVs. Conclusions: novel, promising anti-proliferative agent for UM/MUM. Proteomic profiling cellular/EV candidate pathways elucidating action putative biomarkers UM, that require further examination.

Language: Английский

Citations

4