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Capsaicin-induced apoptosis is regulated by endoplasmic reticulum stress- and calpain-mediated mitochondrial cell death pathways
- Source :
- Toxicology. 264:205-214
- Publication Year :
- 2009
- Publisher :
- Elsevier BV, 2009.
-
Abstract
- Capsaicin, a pungent compound found in hot chili peppers, induces apoptotic cell death in various cell lines, however, the precise apoptosis signaling pathway is unknown. Here, we investigated capsaicin-induced apoptotic signaling in the human breast cell line MCF10A and found that it involves both endoplasmic reticulum (ER) stress and calpain activation. Capsaicin inhibited growth in a dose-dependent manner and induced apoptotic nuclear changes in MCF10A cells. Capsaicin also induced degradation of tumor suppressor p53; this effect was enhanced by the ER stressor tunicamycin. The proteasome inhibitor MG132 completely blocked capsaicin-induced p53 degradation and enhanced apoptotic cell death. Capsaicin treatment triggered ER stress by increasing levels of IRE1, GADD153/Chop, GRP78/Bip, and activated caspase-4. It led to an increase in cytosolic Ca(2+), calpain activation, loss of the mitochondrial transmembrane potential, release of mitochondrial cytochrome c, and caspase-9 and -7 activation. Furthermore, capsaicin-induced the mitochondrial apoptotic pathway through calpain-mediated Bid translocation to the mitochondria and nuclear translocation of apoptosis-inducing factor (AIF). Capsaicin-induced caspase-9, Bid cleavage, and AIF translocation were blocked by calpeptin, and BAPTA and calpeptin attenuated calpain activation and Bid cleavage. Thus, both ER stress- and mitochondria-mediated death pathways are involved in capsaicin-induced apoptosis.
- Subjects :
- Proteasome Endopeptidase Complex
Programmed cell death
Time Factors
Cell Survival
Leupeptins
Apoptotic nuclear changes
Apoptosis
Cysteine Proteinase Inhibitors
Protein Serine-Threonine Kinases
Endoplasmic Reticulum
Toxicology
Cell Line
chemistry.chemical_compound
Stress, Physiological
Endoribonucleases
MG132
Humans
Calcium Signaling
Endoplasmic Reticulum Chaperone BiP
Heat-Shock Proteins
Cell Proliferation
Membrane Potential, Mitochondrial
Dose-Response Relationship, Drug
biology
Calpain
Tunicamycin
Endoplasmic reticulum
Apoptosis Inducing Factor
Cytochromes c
Membrane Proteins
Epithelial Cells
Mitochondria
Cell biology
Enzyme Activation
Protein Transport
chemistry
Caspases
biology.protein
Unfolded protein response
Apoptosis-inducing factor
Capsaicin
Tumor Suppressor Protein p53
Transcription Factor CHOP
BH3 Interacting Domain Death Agonist Protein
Signal Transduction
Subjects
Details
- ISSN :
- 0300483X
- Volume :
- 264
- Database :
- OpenAIRE
- Journal :
- Toxicology
- Accession number :
- edsair.doi.dedup.....4c7a62d545caccd93e7778f710d697b7