Background: Microvesicles are membraned particles produced by different types of cells recently investigated for anticancer purposes. The current study aimed to investigate the effects of human bone marrow mesenchymal stem cell-derived microvesicles (BMSC-MVs) on the multiple myeloma cell line U266. BMSC-MVs were isolated from BMSCs via ultracentrifugation and characterized using transmission electron microscopy (TEM) and dynamic light scattering (DLS). U266 cells were treated with 15, 30, 60, and 120 µg/mL BMSC-MVs for three and seven days and the effects of treatment in terms of viability, cytotoxicity, and DNA damage were investigated via the MTT assay, lactate dehydrogenase (LDH) assay, and 8‑hydroxy-2'-deoxyguanosine (8‑OHdG) measurement, respectively. Moreover, the apoptosis rate of the U266 cells treated with 60 µg/mL BMSC-MVs was also assessed seven days following treatment via flow cytometry. Ultimately, the expression level of BCL2, BAX, and CCND1 by the U266 cells was examined seven days following treatment with 60 µg/mL BMSC-MVs using qRT-PCR.
Results: BMSC-MVs had an average size of ~ 410 nm. According to the MTT and LDH assays, BMSC-MV treatment reduced the U266 cell viability and mediated cytotoxic effects against them, respectively. Moreover, elevated 8‑OHdG levels following BMSC-MV treatment demonstrated a dose-dependent increase of DNA damage in the treated cells. BMSC-MV-treated U266 cells also exhibited an increased apoptosis rate after seven days of treatment. The expression level of BCL2 and CCND1 decreased in the treated cells whereas the BAX expression demonstrated an incremental pattern.
Conclusions: Our findings accentuate the therapeutic benefit of BMSC-MVs against the multiple myeloma cell line U266 and demonstrate how microvesicles could be of therapeutic advantage. Future in vivo studies could further corroborate these findings.
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http://dx.doi.org/10.1007/s00432-024-05822-2 | DOI Listing |
PLoS One
January 2025
Division of Pharmacology, Department of Pharmaceutical Sciences, Faculty of Science, Utrecht University, Utrecht, The Netherlands.
Toll-like receptor (TLRs) activation in multiple myeloma (MM) cells induces heterogeneous functional responses including cell growth and proliferation, survival or apoptosis. These effects have been suggested to be partly due to increase in secretion of cytokines such as IL-6 or IFNα among others from MM cells following TLR activation. However, whether triggering of these receptors also modulates production of immunoglobulin free light chains (FLCs), which largely contribute to MM pathology, has not been investigated in MM cells before.
View Article and Find Full Text PDFPharmaceuticals (Basel)
January 2025
Department of Organic Chemistry and Technology, Faculty of Chemical Technology and Biotechnology, Budapest University of Technology and Economics, Műegyetem rkp. 3, 1111 Budapest, Hungary.
Methylenebisphosphonic derivatives including hydroxy-methylenebisphosphonic species may be of potential biological activity, and a part of them is used in the treatment of bone diseases. Methylenebisphosphonates may be obtained by the Michaelis-Arbuzov reaction of suitably α-substituted methylphosphonates and trialkyl phosphites or phosphinous esters, while the hydroxy-methylene variations are prepared by the Pudovik reaction of α-oxophosphonates and different >P(O)H reagents, such as diethyl phosphite and diarylphosphine oxides. After converting α-hydroxy-benzylphosphonates and -phosphine oxides to the α-halogeno- and α-sulfonyloxy derivatives, they were utilized in the Michaelis-Arbuzov reaction with trialkyl phosphites and ethyl diphenylphosphinite to afford the corresponding bisphosphonate, bis(phosphine oxide) and phosphonate-phosphine oxide derivatives.
View Article and Find Full Text PDFMolecules
January 2025
Department of Organic Chemistry and Technology, Faculty of Chemical Technology and Biotechnology, Budapest University of Technology and Economics, Műegyetem rkp. 3., 1111 Budapest, Hungary.
A series of α-hydroxy-alkylphosphonates and α-hydroxy-alkylphosphine oxides were synthesized by the Pudovik reaction of acetaldehyde and acetone with dialkyl phosphites or diarylphosphine oxides. The additions were performed in three different ways: in liquid phase using triethylamine as the catalyst (1), on the surface of AlO/KF solid catalyst (2), or by a MW-assisted NaCO-catalyzed procedure (3). In most of the cases, our methods were more efficient and more robust than those applied in the literature.
View Article and Find Full Text PDFMolecules
January 2025
Department of Organic Chemistry and Technology, Faculty of Chemical Technology and Biotechnology, Budapest University of Technology and Economics, Műegyetem rkp. 3, 1111 Budapest, Hungary.
Butyl phenyl--phosphinate that is not available commercially was prepared from phenyl--phosphinic acid by three methods: by alkylating esterification (i), by microwave-assisted direct esterification (ii), and unexpectedly, by thermal esterification (iii). Considering the green aspects, selectivity and scalability, the thermal variation seemed to be optimal. However, there was need for prolonged heating.
View Article and Find Full Text PDFInt J Mol Sci
December 2024
Biomedical Centre Martin, Jessenius Faculty of Medicine in Martin, Comenius University Bratislava, 03601 Martin, Slovakia.
Together with chronic inflammation, disturbed magnesium homeostasis is a factor accompanying chronic disease which thus contributes to a reduced quality of human life. In this study, our objective was to examine the possible IL-6-mediated chronic inflammation-dependent regulation of nine magnesiotropic genes encoding for constituents of magnesium homeostasis of the cell. We used three cell lines (HepG2, U-266, and PANC-1), all characterized by high expression of the gene and the presence of a membrane form of IL-6R capable of responding to human IL-6.
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