AI Article Synopsis
Article Abstract
Background: It was reported recently that resveratrol could sensitize a number of cancer cells to the antitumoral effects of some conventional chemotherapy drugs. The current study was designed to investigate whether resveratrol could sensitize leukemic cells to proteasome inhibitors.
Methods: Leukemic cells were treated with MG132 alone or in combination with resveratrol. Cell viability was investigated using MTT assay, and induction of apoptosis and cell cycle distribution was measured using flow cytometry. Western blot and real-time RT-PCR were used to investigate the expression of FOXO1 and p27Kip1. CHIP was performed to investigate the binding of FOXO1 to the p27 Kip1 promoter.
Results: Resveratrol strongly reduced cytotoxic activities of proteasome inhibitors against leukemic cells. MG132 in combination with resveratrol caused cell cycle blockade at G1/S transition via p27Kip1 accumulation. Knockdown of p27Kip1 using siRNA dramatically attenuated the protective effects of resveratrol on cytotoxic actions of proteasome inhibitors against leukemic cells. Resveratrol induced FOXO1 expression at the transcriptional level, while MG132 increased nuclear distribution of FOXO1. MG132 in combination with resveratrol caused synergistic induction of p27Kip1 through increased recruitment of FOXO1 on the p27Kip1 promoter.
Conclusions: Resveratrol may have the potential to negate the cytotoxic effects of proteasome inhibitors via regulation of FOXO1 transcriptional activity and accumulation of p27Kip1.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3066124 | PMC |
| http://dx.doi.org/10.1186/1471-2407-11-99 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
The Many Faces of Philadelphia: A Mature T-Cell Lymphoma with Variant Philadelphia-Translocation and Duplication of the Philadelphia Chromosome.
Hematol Rep
January 2025
Department of 1st Internal Medicine, Medical School, University of Pécs, Ifjúság Str. 13, 7624 Pécs, Hungary.
T-cell prolymphocytic leukemia (T-PLL) is a rare mature T-cell lymphoma that is usually associated with poor prognosis and short overall survival. We present a case of a 61-year-old woman presenting with T-PLL and the leukemic cells harboring (-breakpoint cluster region; -ABL protooncogene 1) fusion transcripts as the result of a variant of t(9;22)(q34;q11) called Philadelphia translocation: t(9;22;18)(q34;q11;q21). Sequencing revealed a rare transcript with an exon 6 breakpoint corresponding to e6a2 transcripts, which has thus far been reported in only 26 cases of leukemias.
View Article and Find Full Text PDFBenzene-induced hematotoxicity enhances the self-renewal ability of HSPCs in Mll-Af9 mice.
Toxicology
January 2025
Key Laboratory of Chemical Safety and Health, National Institute for Occupational Health and Poison Control, Chinese Center for Disease Control and Prevention, Beijing, China; China State Key Laboratory of Trauma, Burn and Combined Injury, China. Electronic address:
Patients with benzene-induced leukemia undergo a continuous transformation from myelosuppression to malignant proliferation. However, the underlying mechanisms in this process remain unknown. Our previous studies have shown that the pathways involved in self-renewal capacity of bone marrow (BM) cells in Mll-Af9 mice exposed to benzene for life are significantly activated after severe blood toxicity.
View Article and Find Full Text PDFFLT3 is genetically essential for ITD-mutated leukemic stem cells but dispensable for human hematopoietic stem cells.
Blood
January 2025
1Princess Margaret Cancer Centre, University Health Network; Toronto, ON M5G 1L7, Canada 14Department of Molecular Genetics, University of Toronto; Toronto, ON, Canada, Canada.
Leukemic stem cells (LSCs) fuel acute myeloid leukemia (AML) growth and relapse, but therapies tailored towards eradicating LSCs without harming normal hematopoietic stem cells (HSCs) are lacking. FLT3 is considered an important therapeutic target due to frequent mutation in AML and association with relapse. However, there has been limited clinical success with FLT3 drug targeting, suggesting either that FLT3 is not a vulnerability in LSC, or that more potent inhibition is required, a scenario where HSC toxicity could become limiting.
View Article and Find Full Text PDFInvestigating resistance to 5-Azacytidine and Venetoclax in PDX models of MDS/AML.
Front Oncol
January 2025
BIOCEV, First Faculty of Medicine, Charles University, Prague, Czechia.
Introduction: Progressing myelodysplastic syndrome (MDS) into acute myeloid leukemia (AML) is an indication for hypomethylating therapy (HMA, 5-Azacytidine (AZA)) and a BCL2 inhibitor (Venetoclax, VEN) for intensive chemotherapy ineligible patients. Mouse models that engraft primary AML samples may further advance VEN + AZA resistance research.
Methods: We generated a set of transplantable murine PDX models from MDS/AML patients who developed resistance to VEN + AZA and compared the differences in hematopoiesis of the PDX models with primary bone marrow samples at the genetic level.
The dynamic interaction of pediatric ALL cells and MSCs: influencing leukemic cell survival and modulating MSC β-catenin expression.
Histochem Cell Biol
January 2025
Department of Histology and Embryology, Faculty of Medicine, Ankara Yildirim Beyazit University, 06800, Ankara, Turkey.
Bone marrow mesenchymal stromal cells (BM-MSCs) are integral components of the bone marrow microenvironment, playing a crucial role in supporting hematopoiesis. Recent studies have investigated the potential involvement of BM-MSCs in the pathophysiology of acute lymphoblastic leukemia (ALL). However, the exact contribution of BM-MSCs to leukemia progression remains unclear because of conflicting findings and limited characterization.
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!