Project description:We previously reported that mebendazole is an effective anti-AML therapeutic and acts via induction of MYB degradation. The present experiemnt was performed in order to uncover pathways of potential resistance in AML cells to mebendazole exposure. A whole genome CRISPR drop-out screen was performed on THP-1 AML cells exposed to 1 micromolar mebendazole or DMSO in order to identify genes that decreased AML sensitivity to this drug.
Project description:We identified mebendazole as a drug to circumvent chemoresistance in hepatoblastoma cell lines that are resistant to cisplatin. In order to identify the mechanistic basis of mebendazole function, we performed gene expression analysis of three mebendazole-treated hepatoblastoma cell lines.
Project description:Histoplasmosis is a frequent mycosis in people living with HIV/AIDS and other immunocompromised hosts. Histoplasmosis has high rates of mortality in these patients if treatment is unsuccessful. Itraconazole and amphotericin B are used to treat histoplasmosis; however, both antifungals have potentially severe pharmacokinetic drug interactions and toxicity. The present study determined the minimal inhibitory and fungicidal concentrations of mebendazole, a drug present in the NIH Clinical Collection, to establish whether it has fungicidal or fungistatic activity against Histoplasma capsulatum. Protein extracts from H. capsulatum yeasts, treated or not with mebendazole, were analyzed by proteomics to understand the metabolic changes driven by this benzimidazole. Mebendazole inhibited the growth of 10 H. capsulatum strains, presenting minimal inhibitory concentrations ranging from 5.0 to 0.08 µM. Proteomics revealed 30 and 18 proteins exclusively detected in untreated and mebendazole-treated H. capsulatum yeast cells, respectively. Proteins related to the tricarboxylic acid cycle, cytoskeleton, and ribosomes were highly abundant in untreated cells. Proteins related to the nitrogen, sulfur, and pyrimidine metabolisms were enriched in mebendazole-treated cells. Furthermore, mebendazole was able to inhibit the oxidative metabolism, disrupt the cytoskeleton, and decrease ribosomal proteins in H. capsulatum. These results suggest mebendazole as a drug to be repurposed for histoplasmosis treatment.
Project description:Monocytic leukemia cell line, THP-1 cells are known to respond to CXCL14. To identfy transcriptional regulation of CXCL14 signalling, we analyse gene expression changed with CXCL14 treatment.
Project description:Monocytic leukemia cell line, THP-1 cells are known to respond to CXCL14. To identfy transcriptional regulation of CXCL14 signalling, we analyse gene expression changed with CXCL14 treatment. THP-1 treated with CXCL14 or PBS treated sample were used.
Project description:In order to understand the consequences of the LPS from different bacterias, we analyzed RNA gene expression profiles in a human myeloid cell line THP-1 cells. RNA-seq transcriptome was analyzed in THP-1 cells treated with LPS from three bacteria B. fungorum, S. marcescens, and P. myrsinacearum.
Project description:THP-1 is a representative leukemia cell line, and has been widely used all around the world since its establishment in Japan in 1980. Differences in THP-1 cells have been reported; however, the THP-1 genomes have not been accurately characterized.