Highlighting Curcumin-Induced Crosstalk between Autophagy and Apoptosis as Supported by Its Specific Subcellular
Francisco J Sala de Oyanguren1, Nathan E Rainey2,3, Aoula Moustapha2
1Laboratory of Cytomics, Joint Research Unit, University of Valencia, Avda. Blasco Ibanez 15, 46010 Valencia and Principe Felipe Research Center, Cerrer d'Eduardo Primo Yufera 3, 46012 Valencia, Spain.
Cells
|February 9, 2020
Summary
Curcumin triggers endoplasmic reticulum (ER) stress and mitochondrial damage, leading to cancer cell death. While autophagy initially attempts to rescue cells, some survivors exhibit a novel proliferation phase.
Area of Science:
- Cell Biology
- Molecular Biology
- Cancer Research
Background:
- Curcumin, derived from turmeric, exhibits anticancer properties.
- The precise mechanisms of curcumin's anticancer effects, particularly its impact on cellular stress pathways, remain incompletely understood.
Purpose of the Study:
- To elucidate the mechanistic aspects of curcumin's effects on endoplasmic reticulum (ER) stress and lysosomal compartments in cancer cells.
- To investigate the role of ER stress, mitochondrial destabilization, and lysosomal permeabilization in curcumin-induced apoptosis.
Main Methods:
- In vitro studies utilizing Image flow cytometry.
- Analysis of ER stress, unfolded protein response, calcium release, mitochondrial integrity, and lysosomal compartment status.
Main Results:
- Curcumin induces ER stress, leading to unfolded protein response and calcium release.
- This destabilizes mitochondria and triggers apoptosis, accompanied by lysosomal membrane permeabilization and caspase-8 activation.
- While autophagy is induced, it fails to rescue all cells, with a subset undergoing a novel proliferation phase.
Conclusions:
- Curcumin-induced cell death involves interconnected pathways of ER stress, mitochondrial dysfunction, and lysosomal damage.
- The interplay between these pathways amplifies cell death, though a small population of cells may survive and proliferate.
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