Apoptosis-Independent Alterations in Membrane Dynamics Induced by Curcumin

Jaruga, Ewa; Sokal, Adam; Chrul, Sławomir; Bartosz, Grzegorz

doi:10.1006/excr.1998.4225

Cited by 75 publications

(61 citation statements)

References 41 publications

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“…Although we have not addressed sites of interaction of curcumin with the NF-B signaling cascade in this study, it is of interest to note that FACS analysis demonstrated that curcumin rapidly associated with components of the cell membrane, suggesting that curcumin could function by interfering with membrane signaling events. A similar conclusion has been reached following studies of the effect of curcumin on erythrocytes, where the authors concluded that curcumin induced apoptosis-independent alterations in membrane dynamics associated with phospholipid scrambling at the plasma and possibly also the mitochondrial cellular membranes (35).…”

Section: Discussionsupporting

confidence: 69%

Curcumin Inhibits Activation of Vγ9Vδ2 T Cells by Phosphoantigens and Induces Apoptosis Involving Apoptosis-Inducing Factor and Large Scale DNA Fragmentation

Cipriani

Borsellino

Knowles

et al. 2001

The Journal of Immunology

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Curcumin, in addition to its role as a spice, has been used for centuries to treat inflammatory disorders. Although the mechanism of action remains unclear, it has been shown to inhibit the activation of NF-κB and AP-1, transcription factors required for induction of many proinflammatory mediators. Due to its low toxicity it is currently under consideration as a broad anti-inflammatory, anti-tumor cell agent. In this study we investigated whether curcumin inhibited the response of γδ T cells to protease-resistant phosphorylated derivatives found in the cell wall of many pathogens. The results showed that curcumin levels ≥30 μM profoundly inhibited isopentenyl pyrophosphate-induced release of the chemokines macrophage inflammatory protein-1α and -1β and RANTES. Curcumin also blocked isopentenyl pyrophosphate-induced activation of NF-κB and AP-1. Commencing around 16 h, treatment with curcumin lead to the induction of cell death that could not be reversed by APC, IL-15, or IL-2. This cytotoxicity was associated with increased annexin V reactivity, nuclear expression of active caspase-3, cleavage of poly(ADP-ribose) polymerase, translocation of apoptosis-inducing factor to the nucleus, and morphological evidence of nuclear disintegration. However, curcumin led to only large scale DNA chromatolysis, as determined by a combination of TUNEL staining and pulse-field and agarose gel electrophoresis, suggesting a predominantly apoptosis-inducing factor-mediated cell death process. We conclude that γδ T cells activated by these ubiquitous Ags are highly sensitive to curcumin, and that this effect may contribute to the anti-inflammatory properties of this compound.

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Section: Discussionsupporting

confidence: 69%

Curcumin Inhibits Activation of Vγ9Vδ2 T Cells by Phosphoantigens and Induces Apoptosis Involving Apoptosis-Inducing Factor and Large Scale DNA Fragmentation

Cipriani

Borsellino

Knowles

et al. 2001

The Journal of Immunology

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“…In some cell lines, the results have even been conflicting, such as in HT-29 human colon cancer cells, that have been noted to be induced into apoptosis by some authors (45), whereas the others noted no effect of curcumin (46). Curcumin, being a hydrophobic molecule (47) passes through the plasma membrane easly into cytosol.…”

Section: Discussionmentioning

confidence: 99%

The interference of rosmarinic acid in the DNA fragmentation induced by osmotic shock

et al. 2007

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The induction of cell death in human erythroleukemic cells (K562) by sorbitol shows the typical apoptotic changes in ultrastructural morphology, including blebbing, chromatin condensation and nuclear membrane breakdown.. Using a cytofluorimetric approach, we found that sorbitol induced production of reactive oxygen species (ROS) followed by DNA fragmentation in leukemic cells. In this study, we investigated effect of curcumin and rosmarinic acid on cell viability in three different cell lines: erythroleukemia K562 , papillary NPA, and anaplastic ARO thyroid cancers. Curcumin was able to induce apoptosis in a concentration-and time dependent manner in three cell lines , while rosmarinic acid was less effective on this process. To examine this possibility in cellular system, this study evaluated the capacities of both compounds acting as antioxidant inhibiting sorbitolinduced apoptosis. K562, NPA and ARO cells were preincubated with 25 µM rosmarinic acid to allow the uptake and then the cell lines were treated with 1 M sorbitol. Afterwards, the cells were subjected to agarose gel electrophoresis to assess the DNA fragmentation.In conclusion, the antioxidant activity of rosmarinic acid is able to inhibit sorbitol-induced apoptosis.

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“…As curcumin displays a very similar low micromolar activity against a number of protozoa in vitro, including Leishmania spp (Saleheen et al, 2002;Changtam et al, 2010a), Giardia lamblia (Pérez-Arriaga et al, 2006), Plasmodium falciparum (Mishra et al, 2008), and Trypanosoma brucei (Nose et al, 1998;Changtam et al, 2010a), the argument of limited specificity is compelling. In this respect, it is of interest to note that curcumin is known to alter membrane fluidity in an apoptosis-independent way (Jaruga et al, 1998;Atsumi et al, 2005;Hung et al, 2008;Ingolfsson et al, 2014).…”

Section: Discussionmentioning

confidence: 99%

Potent Trypanocidal Curcumin Analogs Bearing a Monoenone Linker Motif Act on Trypanosoma brucei by Forming an Adduct with Trypanothione

Alkhaldi

Creek

Ibrahim

et al. 2015

Molecular Pharmacology

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We have previously reported that curcumin analogs with a C 7 linker bearing a C 4 -C 5 olefinic linker with a single keto group at C3 (enone linker) display midnanomolar activity against the bloodstream form of Trypanosoma brucei. However, no clear indication of their mechanism of action or superior antiparasitic activity relative to analogs with the original di-ketone curcumin linker was apparent. To further investigate their utility as antiparasitic agents, we compare the cellular effects of curcumin and the enone linker lead compound 1,7-bis(4-hydroxy-3-methoxyphenyl)hept-4-en-3-one (AS-HK014) here. An AS-HK014-resitant line, trypanosomes adapted to AS-HK014 (TA014), was developed by in vitro exposure to the drug. Metabolomic analysis revealed that exposure to AS-HK014, but not curcumin, rapidly depleted glutathione and trypanothione in the wild-type line, although almost all other metabolites were unchanged relative to control. In TA014 cells, thiol levels were similar to untreated wild-type cells and not significantly depleted by AS-HK014. Adducts of AS-HK014 with both glutathione and trypanothione were identified in AS-HK014-exposed wild-type cells and reproduced by chemical reaction. However, adduct accumulation in sensitive cells was much lower than in resistant cells. TA014 cells did not exhibit any changes in sequence or protein levels of glutathione synthetase and g-glutamylcysteine synthetase relative to wild-type cells. We conclude that monoenone curcuminoids have a different mode of action than curcumin, rapidly and specifically depleting thiol levels in trypanosomes by forming an adduct. This adduct may ultimately be responsible for the highly potent trypanocidal and antiparasitic activity of the monoenone curcuminoids.

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Apoptosis-Independent Alterations in Membrane Dynamics Induced by Curcumin

Cited by 75 publications

References 41 publications

Curcumin Inhibits Activation of Vγ9Vδ2 T Cells by Phosphoantigens and Induces Apoptosis Involving Apoptosis-Inducing Factor and Large Scale DNA Fragmentation

Curcumin Inhibits Activation of Vγ9Vδ2 T Cells by Phosphoantigens and Induces Apoptosis Involving Apoptosis-Inducing Factor and Large Scale DNA Fragmentation

The interference of rosmarinic acid in the DNA fragmentation induced by osmotic shock

Potent Trypanocidal Curcumin Analogs Bearing a Monoenone Linker Motif Act on Trypanosoma brucei by Forming an Adduct with Trypanothione

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