s-1743 has been researched along with Neoplasm-Metastasis* in 1 studies
1 other study(ies) available for s-1743 and Neoplasm-Metastasis
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Esomeprazole inhibits the lysosomal cysteine protease legumain to prevent cancer metastasis.
Legumain is a newly discovered lysosomal cysteine protease that can cleave asparagine bonds and plays crucial roles in regulating immunity and cancer metastasis. Legumain has been shown to be highly expressed in various solid tumors, within the tumor microenvironment and its levels are directly related to tumor metastasis and poor prognosis. Therefore, legumain presents as a potential cancer therapeutic drug target. In this study, we have identified esomeprazole and omeprazole as novel legumain small molecule inhibitors by screening an FDA approved-drug library. These compounds inhibited enzyme activity of both recombinant and endogenous legumain proteins with esomeprazole displaying the highest inhibitory effect. Further molecular docking analysis also indicated that esomeprazole, the S- form of omeprazole had the most stable binding to legumain protein compared to R-omeprazole. Transwell assay data showed that esomeprazole and omeprazole reduced MDA-MB-231 breast cancer cell invasion without effecting cell viability. Moreover, an in vivo orthotopic transplantation nude mouse model study showed that esomeprazole reduced lung metastasis of MDA-MB-231 breast cancer cells. These results indicated that esomeprazole has the exciting potential to be used in anti-cancer therapy by preventing cancer metastasis via the inhibition of legumain enzyme activity. Graphical abstract. Topics: Animals; Anti-Ulcer Agents; Breast Neoplasms; Cell Line, Tumor; Cell Survival; Cysteine Endopeptidases; Cysteine Proteases; Esomeprazole; Female; Humans; Lung Neoplasms; Lysosomes; Mice; Mice, Inbred BALB C; Neoplasm Metastasis; Omeprazole; Xenograft Model Antitumor Assays | 2021 |