Development of a Novel, Potent, and Selective Sialyltransferase Inhibitor for Suppressing Cancer Metastasis

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(8), P. 4283 - 4283

Published: April 12, 2024

Sialyltransferase-catalyzed membrane protein and lipid glycosylation plays a vital role as one of the most abundant post-translational modifications diversification reactions in eukaryotes. However, aberrant sialylation has been associated with cancer malignancy metastasis. Sialyltransferases thus represent emerging targets for development small molecule drugs. Herein, we report inhibitory effects recently discovered lithocholic acid derivative FCW393 on sialyltransferase catalytic activity, integrin sialyation, cancer-associated signal transduction, MDA-MB-231 B16F10 cell migration invasion, vivo studies, tumor growth, metastasis, angiogenesis. showed effective selective inhibition sialyltransferases ST6GAL1 (IC50 = 7.8 μM) ST3GAL3 9.45 relative to ST3GAL1 > 400 ST8SIA4 100 μM). reduced breast melanoma cells dose-dependently downregulated proteins integrin-regulated FAK/paxillin GEF/Rho/ROCK pathways, VEGF-regulated Akt/NFκB/HIF-1α pathway. inhibited 2.6 invasion vitro experiments, studies tumor-bearing mice, size, angiogenesis, metastatic potential. Based its demonstrated selectivity, permeability, relatively low cytotoxicity 55 μM), high efficacy, shows promising potential experimental tool compound lead further novel therapeutic.

Language: Английский

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Focal adhesion kinase-mediated interaction between tumor and immune cells in the tumor microenvironment: implications for cancer-associated therapies and tumor progression

Clinical & Translational Oncology, Journal Year: 2024, Volume and Issue: unknown

Published: Sept. 13, 2024

Language: Английский

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Cytotoxic Activity, Anti-Migration and In Silico Study of Black Ginger (Kaempferia parviflora) Extract against Breast Cancer Cell

Cancers, Journal Year: 2023, Volume and Issue: 15(10), P. 2785 - 2785

Published: May 17, 2023

Metastatic breast cancer remains the leading cause of death in women worldwide. This condition necessitates extensive research to find an effective treatment, one which is natural medicine approach. Kaempferia parviflora (KP) a plant believed possess anticancer properties. Therefore, this study aims determine KP's bioactive compound, cytotoxic, and anti-migration activity highly metastatic cell line model 4T1, also MCF-7 noncancerous NIH-3T3. Maceration with ethanol (EEKP) infusion distilled water (EWKP) was used for extraction. The MTT assay test cytotoxicity, scratch wound healing inhibition migration. Phytochemical profiling EEKP performed using UHPLC-MS, results were studied silico molecular docking. Result showed that had better cytotoxic than EWKP IC50 value 128.33 µg/mL (24 h) 115.09 (48 on 4T1 line, 138.43 124.81 line. Meanwhile, no observed at concentrations ranging from 3-250 concentration 65 µg/mL. Mass Spectrophotometer (MS) structures are 5-Hydroxy-7,4'-dimethoxyflavanone (HDMF), 5-Hydro-7,8,2'-trimethoxyflavanone (HTMF), Retusine, Denbinobin. docking investigated receptors Bcl-2, Bcl-XL, ERK2, FAK, as well their activities. In result indicates HTMF denbinobin compounds responsible EEKP's activity. These two standardized extract can be further potential treatment candidates.

Language: Английский

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PYK2, a hub of signaling networks in breast cancer progression

Trends in Cell Biology, Journal Year: 2023, Volume and Issue: 34(4), P. 312 - 326

Published: Aug. 15, 2023

Language: Английский

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The dual FAK-HDAC inhibitor MY-1259 displays potent activities in gastric cancers in vitro and in vivo

Bioorganic Chemistry, Journal Year: 2022, Volume and Issue: 131, P. 106328 - 106328

Published: Dec. 17, 2022

Language: Английский

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