Curcumin induces crosstalk between autophagy and apoptosis mediated by calcium release from the endoplasmic reticulum, lysosomal destabilization and mitochondrial events

Moustapha, Aoula; Pa, Pérétout; Rainey, Nathan Earl; Sureau, Franck; Gèze, Marc; Jm, Petit; Dewailly, Etienne; Slomianny, Christian; Px, Petit

doi:10.1038/cddiscovery.2015.17

Cited by 117 publications

(148 citation statements)

References 51 publications

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“…However, curcumin has been recognized mainly as an anti-oxidant compound353637. In accordance, a recent study by Moustapha et al 38. revealed that this is the predominant effect at very low doses of curcumin (lower than 1 μM) while at higher concentrations, 10 μM, it starts inducing early events of autophagy and at even higher dosages (>25 μM) it induces apoptosis and endoplasmic reticulum stress causing calcium release, with destabilization of the mitochondrial compartment and promoting tumor cell death3839.…”

Section: Discussionmentioning

confidence: 80%

“…revealed that this is the predominant effect at very low doses of curcumin (lower than 1 μM) while at higher concentrations, 10 μM, it starts inducing early events of autophagy and at even higher dosages (>25 μM) it induces apoptosis and endoplasmic reticulum stress causing calcium release, with destabilization of the mitochondrial compartment and promoting tumor cell death3839. This hormetic characteristic of curcumin has been detailed using a tumor cell line namely, hepatocellular carcinoma Huh-7 cells38. Nonetheless, molecular effects of curcumin on complex cell systems might most likely be cell-type specific in a concentration and time-dependent manner.…”

Section: Discussionmentioning

confidence: 99%

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Curcumin: A multi-target disease-modifying agent for late-stage transthyretin amyloidosis

Ferreira

Gonçalves

Saraiva

et al. 2016

Sci Rep

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Transthyretin amyloidoses encompass a variety of acquired and hereditary diseases triggered by systemic extracellular accumulation of toxic transthyretin aggregates and fibrils, particularly in the peripheral nervous system. Since transthyretin amyloidoses are typically complex progressive disorders, therapeutic approaches aiming multiple molecular targets simultaneously, might improve therapy efficacy and treatment outcome. In this study, we evaluate the protective effect of physiologically achievable doses of curcumin on the cytotoxicity induced by transthyretin oligomers in vitro by showing reduction of caspase-3 activity and the levels of endoplasmic reticulum-resident chaperone binding immunoglobulin protein. When given to an aged Familial Amyloidotic Polyneuropathy mouse model, curcumin not only reduced transthyretin aggregates deposition and toxicity in both gastrointestinal tract and dorsal root ganglia but also remodeled congophilic amyloid material in tissues. In addition, curcumin enhanced internalization, intracellular transport and degradation of transthyretin oligomers by primary macrophages from aged Familial Amyloidotic Polyneuropathy transgenic mice, suggesting an impaired activation of naïve phagocytic cells exposed to transthyretin toxic intermediate species. Overall, our results clearly support curcumin or optimized derivatives as promising multi-target disease-modifying agent for late-stage transthyretin amyloidosis.

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Section: Discussionmentioning

confidence: 80%

Section: Discussionmentioning

confidence: 99%

Curcumin: A multi-target disease-modifying agent for late-stage transthyretin amyloidosis

Ferreira

Gonçalves

Saraiva

et al. 2016

Sci Rep

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“…69. More detailed explanations are given in supplementary Materials and methods for cathepsins and calpain, respectively.…”

Section: Methodsmentioning

confidence: 99%

Synergistic cellular effects including mitochondrial destabilization, autophagy and apoptosis following low-level exposure to a mixture of lipophilic persistent organic pollutants

Rainey

Šarić

Leberre

et al. 2017

Sci Rep

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Humans are exposed to multiple exogenous environmental pollutants. Many of these compounds are parts of mixtures that can exacerbate harmful effects of the individual mixture components. 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), is primarily produced via industrial processes including incineration and the manufacture of herbicides. Both endosulfan and TCDD are persistent organic pollutants which elicit cytotoxic effects by inducing reactive oxygen species generation. Sublethal concentrations of mixtures of TCDD and endosulfan increase oxidative stress, as well as mitochondrial homeostasis disruption, which is preceded by a calcium rise and, in fine, induce cell death. TCDD+Endosulfan elicit a complex signaling sequence involving reticulum endoplasmic destalilization which leads to Ca2+ rise, superoxide anion production, ATP drop and late NADP(H) depletion associated with a mitochondrial induced apoptosis concomitant early autophagic processes. The ROS scavenger, N-acetyl-cysteine, blocks both the mixture-induced autophagy and death. Calcium chelators act similarly and mitochondrially targeted anti-oxidants also abrogate these effects. Inhibition of the autophagic fluxes with 3-methyladenine, increases mixture-induced cell death. These findings show that subchronic doses of pollutants may act synergistically. They also reveal that the onset of autophagy might serve as a protective mechanism against ROS-triggered cytotoxic effects of a cocktail of pollutants in Caco-2 cells and increase their tumorigenicity.

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“…Curcumin can also be excited at 488 nm, with a lower fluorescent yield emission in the 500-530 nm range, for detection by flow cytometry and confocal microscopy. Curiously, this has rarely been used for curcumin imaging at the cellular level (8,9). Curcumin is a hydrophobic molecule with a log P value of 3.0 at neutral pH (10).…”

confidence: 99%

“…In this regard, the depletion of glutathione suggests that curcumin could act as a pro-oxidant contributor in some conditions (17). At low concentrations, curcumin reacts as an antioxidant, but acquires pro-oxidant properties above 20 µM, thus revealing its hormetic behavior (8,18). Curcumin is a pleiotropic molecule which interacts with multiple targets involved in inflammatory reactions, such as tumor necrosis factor-alpha (TNFα) and interleukins (ILs) (19).…”

confidence: 99%

Highlighting curcumin-induced crosstalk between autophagy and apoptosis: A biochemical approach coupling impedancemetry, imaging, and flow cytometry

Oyanguren

Rainey

Moustapha

et al. 2019

Preprint

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These authors contributed equally.Curcumin, a major active component of turmeric (Curcuma longa, L.), is known to have various effects on both healthy and cancerous tissues. In vitro studies suggest that curcumin inhibits cancer cell growth by activating apoptosis, but the mechanism underlying the anticancer effects of curcumin is still unclear. Since there is a consensus about endoplasmic reticulum (ER) stress being involved in the cytotoxicity of many natural compounds, we investigated by Amnis ® Imaging flow cytometry the mechanistic aspects of curcumin's destabilization of the ER, but also the status of the lysosomal compartment involved in curcumin-associated apoptosis. Curcumin induces ER stress thereby causing an unfolded protein response (UPR) and calcium release which destabilize the mitochondrial compartment and induce apoptosis. These events are also associated with secondary lysosomal membrane permeabilization and activation of caspase-8, mediated by activation of cathepsins and calpains. We previously showed that sequence lead to the generation of truncated tBid and disruption of mitochondrial homeostasis. These two pathways of different intensities and momentum converge towards an amplification of cell death that still needs to be studied in more detail. It has been suggested that it may be possible to exploit autophagy for cancer therapy. There is a complex interplay involving early autophagy as soon as mitochondria produce superoxide anions and hydrogen peroxide. Treatments with 10 µM to 20 µM curcumin induce autophagosome formation, while only early events of cell death are detectable.In the present study, curcumin-induced autophagy failed to rescue all cells since most cells underwent type II cell death following initial autophagic processes. However, a small number of cells blocked in the cell cycle escaped and were rescued to give rise to a novel proliferation phase. Curcumin | cell death | autophagy | apoptosis | ROS | Calcium | Stress | Mitochondria | Endoplasmic reticulum | cancer |

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Curcumin induces crosstalk between autophagy and apoptosis mediated by calcium release from the endoplasmic reticulum, lysosomal destabilization and mitochondrial events

Cited by 117 publications

References 51 publications

Curcumin: A multi-target disease-modifying agent for late-stage transthyretin amyloidosis

Curcumin: A multi-target disease-modifying agent for late-stage transthyretin amyloidosis

Synergistic cellular effects including mitochondrial destabilization, autophagy and apoptosis following low-level exposure to a mixture of lipophilic persistent organic pollutants

Highlighting curcumin-induced crosstalk between autophagy and apoptosis: A biochemical approach coupling impedancemetry, imaging, and flow cytometry

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