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Involvement of extrinsic and intrinsic apoptotic pathways together with endoplasmic reticulum stress in cell death induced by naphthylchalcones in a leukemic cell line: advantages of multi-target action
- Source :
- Toxicology in vitro : an international journal published in association with BIBRA. 28(5)
- Publication Year :
- 2013
-
Abstract
- Chalcones, naturally occurring open-chain flavonoids abundant in plants, have demonstrated anticancer activity in multiple tumor cells. In a previous work, the potential anticancer activity of three naphthylchalcones named R7, R13 and R15 was shown. In this study, the mechanism of actions of these chalcones was originally shown. The chalcones presented concentration and time-dependent cytotoxicity. To determine the type of cell death induced by chalcones, we assessed a series of assays including measurements of the caspase-8, -9 and -12 activities, expression of important apoptosis-related genes and proteins, changes in the cell calcium concentration and cytochrome c release. The activities of caspase-8, -9 and -12 increased after the treatment of L1210 cells with the three compounds. Chalcones R7 and R13 induced an increase of pro-apoptotic proteins Bax, Bid and Bak (only chalcone R13), as well as a decrease in anti-apoptotic Bcl-2 expression. These chalcones also induced an increase in Fas and a decrease in p21 and p53 expression. Chalcone R15 seems to act by a different mechanism to promote cell death, as it did not change the mitochondrion-related proteins, nor did it induce the cytochrome c release. All compounds induced an increase in cell calcium concentration and an increase in CHOP expression, which together with an increase in caspase-12 activity, suggest that chalcones could induce an endoplasmic reticulum (ER) stress. Taken together, these results suggest that chalcones induce apoptosis by different pathways, being an interesting strategy to suggest for cancer therapy.
- Subjects :
- Cyclin-Dependent Kinase Inhibitor p21
Programmed cell death
Chalcone
Gene Expression
Antineoplastic Agents
Apoptosis
Biology
Toxicology
chemistry.chemical_compound
Mice
Chalcones
Cell Line, Tumor
Animals
fas Receptor
Cytotoxicity
Vero Cells
Leukemia
Cell Death
Endoplasmic reticulum
Cytochrome c
Intrinsic apoptosis
Cell Cycle
Cytochromes c
General Medicine
Endoplasmic Reticulum Stress
Cell biology
Biochemistry
chemistry
Cell culture
biology.protein
NIH 3T3 Cells
Extrinsic apoptosis
Calcium
Tumor Suppressor Protein p53
Apoptosis Regulatory Proteins
Subjects
Details
- ISSN :
- 18793177
- Volume :
- 28
- Issue :
- 5
- Database :
- OpenAIRE
- Journal :
- Toxicology in vitro : an international journal published in association with BIBRA
- Accession number :
- edsair.doi.dedup.....696172bdc308e3e9cf2f6d09202009fd