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Cellular and molecular mechanisms activating the cell death processes by chalcones: Critical structural effects
Pierre Champelovier1, Xavier Chauchet, Florence Hazane-Puch
1Laboratoire de Cytologie, Département d'Anatomie et de Cytologie Pathologiques, Institut de Biologie et de Pathologie, Centre Hospitalier Universitaire de Grenoble, Hôpital A. Michallon, CS10217, 38043 Grenoble cedex 09, France.
Summary
Two chalcones, despite structural similarity, exhibit distinct anticancer mechanisms against glioblastoma. Chalcone A triggers apoptosis, while Chalcone B induces ROS-related autophagy, highlighting structure-activity relationships in cancer therapy.
Area of Science:
- Biochemistry
- Molecular Biology
- Pharmacology
Background:
- Chalcones are natural compounds with diverse pharmacological properties.
- They share a common 1,3-diphenylpropenone structure.
- Understanding their anticancer mechanisms is crucial for drug development.
Purpose of the Study:
- To investigate the distinct mechanistic pathways of two structurally similar chalcones (A and B) in glioblastoma cells.
- To elucidate how minor structural variations influence anticancer effects.
- To provide evidence for differential cell death induction.
Main Methods:
- Glioblastoma cell lines were treated with chalcones A and B.
- Apoptosis (Type I PCD) and autophagy (Type II PCD) were assessed.
- Caspase activation, cell cycle regulators (CDK1/cyclin B), mitochondrial potential (ΔΨm), reactive oxygen species (ROS), and protein synthesis were analyzed.
- Expression of apoptosis regulators (Bax/Bcl2) and proliferation markers (Ki67, CD71) were measured.
Main Results:
- Chalcone A induced apoptosis via caspase-3, -8, and -9 activation, increased CDK1/cyclin B, and decreased ΔΨm.
- Chalcone B triggered ROS-related autophagy, independent of caspases and protein synthesis.
- Both chalcones upregulated Bax/Bcl2 ratios and downregulated Ki67 and CD71.
- Significant mechanistic differences were observed despite structural similarity.
Conclusions:
- Chalcones A and B exhibit distinct anticancer mechanisms against glioblastoma.
- Chalcone A promotes apoptosis, while Chalcone B induces autophagy.
- These findings underscore the critical role of subtle structural modifications in determining the mode of cell death induced by chalcones.
Keywords:
(1)H NMR1,1,3,3-tetraethoxypropane2′,7′-dichlorofluorescein diacetate3,3′ dihexyloxacarbocyanine iodideATGApoptosisAutophagyBCRPBSABakBaxBcl-2 homologous antagonist killerBcl-2 interacting mediator of cell deathBcl-2-associated X proteinBimCATCCDCDC25CDKCaspasesChalconesDCFDADHRDMSODiOC6EDTAERK1/2GPX1HPLCHRPT1MDAMDCMFIMGGMIMTP or ΔΨmN-acetylcysteinNACNADPHNHNBCNHSFP-glycoproteinP-gpPBSPCDROSTBATEPautophagy related genesbovine serum albuminebreast cancer resistance proteincatalasecell division cycle 25charge-coupled devicecheckpoint kinase 2chk2cyclin dependent kinasedihydrorhodamine-123dimethylsulfoxideethylenediaminetetraacetic acidextracellular signal-regulated kinase 1/2glutathione peroxidase 1high performance liquid chromatographyhydrogen-1 nuclear magnetic resonancehypoxanthine phosphoribosyltransferase 1mTORmalondialdehydemammalian target of Rapamycin (mTOR)may grunwald giemsamean fluorescence intensitymitochondrial transmembrane potentialmitotic indexmonodansylcadaverinenicotinamide adenine dinucleotide phosphatenormal human nucleated blood cellsnormal human skin fibroblastsphosphate buffered salineprogrammed cell deathreactive oxygen speciesthiobarbituric acid
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