Cellular and molecular mechanisms activating the cell death processes by chalcones: Critical structural effects

Abstract

Chalcones are naturally occurring compounds with diverse pharmacological activities. Chalcones derive from the common structure: 1,3-diphenylpropenone. The present study aims to better understand the mechanistic pathways triggering chalcones anticancer effects and providing evidences that minor structural difference could lead to important difference in mechanistic effect. We selected two recently investigated chalcones (A and B) and investigated them on glioblastoma cell lines. It was found that chalcone A induced an apoptotic process (type I PCD), via the activation of caspase-3, -8 and -9. Chalcone A also increased CDK1/cyclin B ratios and decreased the mitochondrial transmembrane potential (ΔΨm). Chalcone B induced an autophagic cell death process (type II PCD), ROS-related but independent of both caspases and protein synthesis. Both chalcones increased Bax/Bcl2 ratios and decreased Ki67 and CD71 antigen expressions. The present investigation reveals that despite the close structure of chalcones A and B, significant differences in mechanism of effect were found.

Keywords: (1)H NMR; 1,1,3,3-tetraethoxypropane; 2′,7′-dichlorofluorescein diacetate; 3,3′ dihexyloxacarbocyanine iodide; ATG; Apoptosis; Autophagy; BCRP; BSA; Bak; Bax; Bcl-2 homologous antagonist killer; Bcl-2 interacting mediator of cell death; Bcl-2-associated X protein; Bim; CAT; CCD; CDC25; CDK; Caspases; Chalcones; DCFDA; DHR; DMSO; DiOC6; EDTA; ERK1/2; GPX1; HPLC; HRPT1; MDA; MDC; MFI; MGG; MI; MTP or ΔΨm; N-acetylcystein; NAC; NADPH; NHNBC; NHSF; P-glycoprotein; P-gp; PBS; PCD; ROS; TBA; TEP; autophagy related genes; bovine serum albumine; breast cancer resistance protein; catalase; cell division cycle 25; charge-coupled device; checkpoint kinase 2; chk2; cyclin dependent kinase; dihydrorhodamine-123; dimethylsulfoxide; ethylenediaminetetraacetic acid; extracellular signal-regulated kinase 1/2; glutathione peroxidase 1; high performance liquid chromatography; hydrogen-1 nuclear magnetic resonance; hypoxanthine phosphoribosyltransferase 1; mTOR; malondialdehyde; mammalian target of Rapamycin (mTOR); may grunwald giemsa; mean fluorescence intensity; mitochondrial transmembrane potential; mitotic index; monodansylcadaverine; nicotinamide adenine dinucleotide phosphate; normal human nucleated blood cells; normal human skin fibroblasts; phosphate buffered saline; programmed cell death; reactive oxygen species; thiobarbituric acid.