In this study, we show that adenosine monophosphate-activated protein kinase (AMPK) is expressed and activated in multiple myeloma cells. The inhibition of AMPK induced growth arrest and reduction of cell viability in the cell viability assay using the water-soluble tetrazolium salt 4-[3-(4-iodophenyl)-2-(4-nitrophenyl)-2H-5-tetrazolio]-1,3-benzene disulfonate (WST-1 assay). Induction of apoptosis was determined by annexin-V and propidium iodide staining. The prevention of apoptosis using the pancaspase inhibitor ZVAD-fmk and caspase-3 cleavage upon incubation with the AMPK inhibitor (AMPKI) is shown. Furthermore, incubation of myeloma cells with AMPKI resulted in the downregulation of pAMPK, Mcl-1 and Bcl-xL. Coincubation of AMPKI and melphalan led to a strong additional increase of apoptosis in myeloma cells. We conclude that AMPKI has a strong antimyeloma activity in vitro and represents a new targeted strategy in the treatment of multiple myeloma.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1097/CAD.0b013e32801416b6 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
A Challenging Case of IgG4-Related Kidney Disease Accompanied With Positive Serologic Tests of Lupus Erythematosus.
Nephrology (Carlton)
January 2025
Division of Nephrology, Department of Internal Medicine, Faculty of Medicine, Thammasat University, Pathumthani, Thailand.
The case report presents a male patient in his mid-60s with a history of hypertension, benign prostatic hyperplasia and chronic kidney disease (CKD). He presented with gradually increasing serum creatinine levels and hyperglobulinemia, leading to suspicion of multiple myeloma. However, subsequent testing revealed features consistent with systemic lupus erythematosus (SLE) and IgG4-related kidney disease (IgG4-RKD).
View Article and Find Full Text PDFThe Impact of Cell-Intrinsic STAT6 Protein on Donor T Cell-Mediated Graft-Versus-Tumor Effect.
Int J Mol Sci
December 2024
Department of Internal Medicine, Division of Gastroenterology and Hepatology, Carver College of Medicine, University of Iowa, Iowa City, IA 52242, USA.
Bone marrow transplantation (BMT) is mainly performed to restore an anti-tumor immune response, called the graft-versus-tumor (GVT) effect, against leukemia, myeloma and lymphoma. This GVT reactivity is driven by donor T cells, and it can also cause lethal graft-versus-host disease (GVHD). We previously demonstrated that the colonization of mice with helminths preserves the GVT response while suppressing GVHD.
View Article and Find Full Text PDFEpigenetic drug screening identifies enzyme inhibitors A-196 and TMP-269 as novel regulators of sprouting angiogenesis.
Sci Rep
January 2025
A.I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, Kuopio, Finland.
Epigenetic therapy has gained interest in treating cardiovascular diseases, but preclinical studies often encounter challenges with cell-type-specific effects or batch-to-batch variation, which have limited identification of novel drug candidates targeting angiogenesis. To address these limitations and improve the reproducibility of epigenetic drug screening, we redesigned a 3D in vitro fibrin bead assay to utilize immortalized human aortic endothelial cells (TeloHAECs) and screened a focused compound library with 105 agents. Compared to the established model using primary human umbilical vein endothelial cells, TeloHAECs needed a higher-density fibrin gel for optimal sprouting, successfully forming sprouts under both normoxic and hypoxic cell culture conditions.
View Article and Find Full Text PDFCAR-T Therapy Beyond B-Cell Hematological Malignancies.
Cells
January 2025
Hematology, St. Eugenio Hospital, ASL Roma2, 00144 Rome, Italy.
Despite the advances of CAR-T cells in certain hematological malignancies, mostly from B-cell derivations such as non-Hodgkin lymphomas, acute lymphoblastic leukemia and multiple myeloma, a significant portion of other hematological and non-hematological pathologies can benefit from this innovative treatment, as the results of clinical studies are demonstrating. The clinical application of CAR-T in the setting of acute T-lymphoid leukemia, acute myeloid leukemia, solid tumors, autoimmune diseases and infections has encountered limitations that are different from those of hematological B-cell diseases. To overcome these restrictions, strategies based on different molecular engineering platforms have been devised and will be illustrated below.
View Article and Find Full Text PDFIn Vitro 3D Models of Haematological Malignancies: Current Trends and the Road Ahead?
Cells
January 2025
DIMEAS, Politecnico di Torino, C.so Duca degli Abruzzi 24, 10129 Torino, Italy.
Haematological malignancies comprise a diverse group of life-threatening systemic diseases, including leukaemia, lymphoma, and multiple myeloma. Currently available therapies, including chemotherapy, immunotherapy, and CAR-T cells, are often associated with important side effects and with the development of drug resistance and, consequently, disease relapse. In the last decades, it was largely demonstrated that the tumor microenvironment significantly affects cancer cell proliferation and tumor response to treatment.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!