With the advent of senolytic agents capable of selectively removing senescent cells in old tissues, the perception of age-associated diseases has been changing from being an inevitable to a preventable phenomenon of human life. In the search for materials with senolytic activity from natural products, six new flavonostilbenes (-), three new phenylethylchromanones (-), three new phenylethylchromones (-), and four known compounds (-) were isolated from the roots of . The chemical structures of these isolated compounds were determined based on the interpretation of spectroscopic data, including 1D and 2D NMR, ECD, and HRMS. The absolute configuration of compound was also determined by a Mosher ester analysis and ECD calculations. Compounds - were shown to selectively destroy senescent cells, and the promoter activity of p16INK4A, a representative senescence marker, was reduced significantly by compound . The present results suggest the potential activity of flavonostilbene and phenylethylchromanone skeletons from . as new senolytics.
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http://dx.doi.org/10.1021/acs.jnatprod.0c00885 | DOI Listing |
Trends Cancer
December 2024
Department of Molecular, Cell, and Cancer Biology, University of Massachusetts Chan Medical School, Worcester, MA, USA; Immunology and Microbiology Program, University of Massachusetts Chan Medical School, Worcester, MA, USA; Cancer Center, University of Massachusetts Chan Medical School, Worcester, MA, USA. Electronic address:
Chronic damage following oncogene induction or cancer therapy can produce cellular senescence. Senescent cells not only exit the cell cycle but communicate damage signals to their environment that can trigger immune responses. Recent work has revealed that senescent tumor cells are highly immunogenic, leading to new ways to activate antitumor immunosurveillance and potentiate T cell-directed immunotherapies.
View Article and Find Full Text PDFDiseases
December 2024
Division of Gastroenterology and Hepatology, Graduate School of Medical and Dental Sciences, Niigata University, Niigata 951-9510, Japan.
Metabolic dysfunction-associated steatotic liver disease (MASLD) causes cellular senescence due to oxidative stress, endoplasmic reticulum stress, and ectopic fat deposition in the liver. Recently, dasatinib, an antitumor agent, and quercetin, a dietary supplement, were combined as a senolytic drug to eliminate senescent cells. Thus, this study aimed to examine the effects of dasatinib and quercetin administration on removing senescent cells and their therapeutic effects on MASLD in a medaka MASLD model.
View Article and Find Full Text PDFBioessays
December 2024
CHU Sainte-Justine Research Center, Montreal, Quebec, Canada.
Myotonic dystrophy type 1 (DM1) is considered a progeroid disease (i.e., causing premature aging).
View Article and Find Full Text PDFProc Natl Acad Sci U S A
December 2024
Division of Molecular Carcinogenesis, Oncode Institute, The Netherlands Cancer Institute, Amsterdam 1066 CX, The Netherlands.
Drugs that eliminate senescent cells, senolytics, can be powerful when combined with prosenescence cancer therapies. Using a CRISPR/Cas9-based genetic screen, we identify here SLC25A23 as a vulnerability of senescent cancer cells. Suppressing SLC25A23 disrupts cellular calcium homeostasis, impairs oxidative phosphorylation, and interferes with redox signaling, leading to death of senescent cells.
View Article and Find Full Text PDFChemistry
December 2024
Wroclaw Medical University: Uniwersytet Medyczny im Piastow Slaskich we Wroclawiu, Department of Pharmacognosy and Herbal Medicines, Borowska 211A, 50-556, Wroclaw, POLAND.
Targeting senescent cells and the factors that accelerate this pathological state has recently emerged as a novel field in medicinal chemistry. As attention shifts to synthetic substances, studies on natural agents are often overlooked. In this paper, we present a detailed computational modeling study that encompasses quantum mechanics and molecular dynamics to elucidate the senotherapeutic activity of fisetin.
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