HIF-1α is involved in the carcinogenesis and progression of multiple types of cancer. However, the precise role of HIF-1α is unclear in multiple myeloma. Through the qRT-PCR and CCK-8 assays, we demonstrated that silencing the expression of HIF-1α and Mcl-1, MM proliferation can be decreased and apoptosis can be induced. Next, using the GEO database, we found that Mcl-1 was increased in MMs. Mcl-1 overexpression counterbalanced the tumor suppressing effect of siHIF-1α on MM apoptosis. Additionally, HIF-1α acting as a transcription factor, could directly target the promoter region of Mcl-1 to promote Mcl-1 expression. Based on the experimental result, our findings strongly suggest that HIF-1α regulated the progression of MMs by directly targeting the Mcl-1.
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J Exp Clin Cancer Res
January 2025
Cancer Biology Graduate Program, Wayne State University School of Medicine, Detroit, MI, 48201, USA.
Background: Venetoclax + azacitidine is a frontline treatment for older adult acute myeloid leukemia (AML) patients and a salvage therapy for relapsed/refractory patients who have been treated with intensive chemotherapy. While this is an important treatment option, many patients fail to achieve complete remission and of those that do, majority relapse. Leukemia stem cells (LSCs) are believed to be responsible for AML relapse and can be targeted through oxidative phosphorylation reduction.
View Article and Find Full Text PDFAngew Chem Int Ed Engl
January 2025
Department of Chemistry, National University of Singapore, Singapore, 117543, Singapore.
Targeted covalent inhibitors (TCIs) play an essential role in the fields of kinase research and drug discovery. TCI strategies to target more common amino acid side-chains have yet to be demonstrated. Targeting other amino acids would also expand the pharmaceutical industry's toolbox for targeting other tough-to-drug proteins.
View Article and Find Full Text PDFInt J Mol Sci
December 2024
Unidad de Investigación Médica en Farmacología, UMAE Hospital de Especialidades, Centro Médico Nacional Siglo XXI, Instituto Mexicano del Seguro Social, Mexico City CP 06720, Mexico.
The Annona genus contains some species used in Mexican traditional medicine for the treatment cancer, including . The present study aimed to investigate the anticancer activity of caryophyllene oxide (CO) isolated from using in vivo, in vitro, and in silico approaches. The identification of CO was performed using gas chromatography-mass spectroscopy and NMR methods.
View Article and Find Full Text PDFCNS Neurosci Ther
January 2025
Department of Neurology, School of Medicine, Guangzhou First People's Hospital, South China University of Technology, Guangzhou, China.
Objective: This study aims to investigate how the E3 ubiquitin ligase LITAF influences mitochondrial autophagy by modulating MCL-1 ubiquitination, and its role in the development of epilepsy.
Methods: Employing single-cell RNA sequencing (scRNA-seq) to analyze brain tissue from epilepsy patients, along with high-throughput transcriptomics, we identified changes in gene expression. This was complemented by in vivo and in vitro experiments, including protein-protein interaction (PPI) network analysis, western blotting, and behavioral assessments in mouse models.
Cell Death Differ
January 2025
Dana Farber Cancer Institute, Boston, MA, USA.
Cellular senescence contributes to a variety of pathologies associated with aging and is implicated as a cellular state in which cancer cells can survive treatment. Reported senolytic drug treatments act through varying molecular mechanisms, but heterogeneous efficacy across the diverse contexts of cellular senescence indicates a need for predictive biomarkers of senolytic activity. Using multi-parametric analyses of commonly reported molecular features of the senescent phenotype, we assayed a variety of models, including malignant and nonmalignant cells, using several triggers of senescence induction and found little univariate predictive power of these traditional senescence markers to identify senolytic drug sensitivity.
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