Cardiolipin mediates curcumin interactions with mitochondrial membranes

Ben-Zichri, Shani; Kolusheva, Sofiya; Danilenko, Michael; Ossikbayeva, Saniya; Stabbert, William J.; Poggio, Juan Lucas; Stein, David E.; Orynbayeva, Zulfiya; Jelinek, Raz

doi:10.1016/j.bbamem.2018.10.016

Cited by 12 publications

(16 citation statements)

References 41 publications

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“…In addition, their mitochondrial membrane characteristics, e.g., variation of lipid content or the degree of saturation of acyl chains [86], may also differ. Earlier, using model membranes mimicking the mitochondria lipid bilayer we demonstrated a high affinity of CUR to cardiolipin, the mitochondria-unique phospholipid [87]. This in part explains the known curcumin's protonophoric activity [88] and overall potential benefits in the treatment of broad range of metabolic diseases and conditions with key involvement of mitochondria.…”

Section: Discussionmentioning

confidence: 88%

Curcumin and Carnosic Acid Cooperate to Inhibit Proliferation and Alter Mitochondrial Function of Metastatic Prostate Cancer Cells

et al. 2021

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Anticancer activities of plant polyphenols have been demonstrated in various models of neoplasia. However, evidence obtained in numerous in vitro studies indicates that proliferation arrest and/or killing of cancer cells require quite high micromolar concentrations of polyphenols that are difficult to reach in vivo and can also be (geno)toxic to at least some types of normal cells. The ability of certain polyphenols to synergize with one another at low concentrations can be used as a promising strategy to effectively treat human malignancies. We have recently reported that curcumin and carnosic acid applied at non-cytotoxic concentrations synergistically cooperate to induce massive apoptosis in acute myeloid leukemia cells, but not in normal hematopoietic and non-hematopoietic cells, via sustained cytosolic calcium overload. Here, we show that the two polyphenols can also synergistically suppress the growth of DU145 and PC-3 metastatic prostate cancer cell cultures. However, instead of cell killing, the combined treatment induced a marked inhibition of cell proliferation associated with G0/G1 cell cycle arrest. This was preceded by transient elevation of cytosolic calcium levels and prolonged dissipation of the mitochondrial membrane potential, without generating oxidative stress, and was associated with defective oxidative phosphorylation encompassing mitochondrial dysfunction. The above effects were concomitant with a significant downregulation of mRNA and protein expression of the oncogenic kinase SGK1, the mitochondria-hosted mTOR component. In addition, a moderate decrease in SGK1 phosphorylation at Ser422 was observed in polyphenol-treated cells. The mTOR inhibitor rapamycin produced a similar reduction in SGK1 mRNA and protein levels as well as phosphorylation. Collectively, our findings suggest that the combination of curcumin and carnosic acid at potentially bioavailable concentrations may effectively target different types of cancer cells by distinct modes of action. This and similar combinations merit further exploration as an anticancer modality.

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Section: Discussionmentioning

confidence: 88%

Curcumin and Carnosic Acid Cooperate to Inhibit Proliferation and Alter Mitochondrial Function of Metastatic Prostate Cancer Cells

et al. 2021

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“…Curcumin has been proven to have similar properties. The compound affects membrane structure (Barry et al, 2009) by incorporation into lipid bilayer (Ben-Zichri et al, 2019), modulates the lipid raft domains (Tsukamoto et al, 2014), affects the lipid membrane making it thinner, and weakens its elasticity (Hung et al, 2008). According to these findings, the tested antioxidants may have altered the physical properties of cell membrane resulting in its increased stability in lower temperature and decreased permeabilization, which was measured in YO-PRO-1 assay directly after the balloon flight and highlighted in CLSM analysis.…”

Section: Discussionmentioning

confidence: 99%

“…Regarding the antioxidant-mediated handling with extreme conditions, it is worth to note the impact of the compounds such as cinnamon (Azab et al, 2011), curcumin (Hung et al, 2008; Barry et al, 2009; Tsukamoto et al, 2014; Ben-Zichri et al, 2019), plant flavonoids (Oteiza et al, 2005; Ajdžanović et al, 2013; Tarahovsky et al, 2014), or polyphenols (Cyboran et al, 2012) on the biophysical properties of cell membrane, which could play a protective role in a rapidly changing environment.…”

Section: Introductionmentioning

confidence: 99%

The Cytoprotective Role of Antioxidants in Mammalian Cells Under Rapidly Varying UV Conditions During Stratospheric Balloon Campaign

et al. 2019

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The current age of dynamic development of the space industry brings the mankind closer to routine manned space flights and space tourism. This progress leads to a demand for intensive astrobiological research aimed at improving strategies of the pharmacological protection of the human cells against extreme conditions. Although routine research in space remains out of our reach, it is worth noticing that the unique severe environment of the Earth’s stratosphere has been found to mimic subcosmic conditions, giving rise to the opportunity to use the stratospheric surface as a research model for the astrobiological studies. Our study included launching into the stratosphere a balloon containing mammalian normal and cancer cells treated with various compounds to examine whether these substances are capable of protecting the cells against stress caused by rapidly varying temperature, pressure, and radiation, especially UV. Owing to oxidative stress caused by irradiation and temperature shock, we used natural compounds which display antioxidant properties, namely, catechin isolated from green tea, honokiol derived from magnolia, curcumin from turmeric, and cinnamon extract. “After-flight” laboratory tests have shown the most active antioxidants as potential agents which can minimize harmful impact of extreme conditions on human cells.

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“…These wide array of health benefits are mainly attributed to curcumin’s ability to modulate the function and expression of multiple intracellular targets, specifically transcription factors, antiapoptotic proteins, and membrane proteins, and to scavenge reactive oxygen species. , In addition, curcumin can change the properties of cell membranes and hence indirectly effect the membrane proteins. Experimental studies have revealed that curcumin can localize in the membrane, , increases the membrane permeability, , induces membrane thinning effect on a concentration dependent manner, and leads to apoptosis-like reversible changes in plasma membrane asymmetry . In spite of curcumin’s known membrane activity, the details of molecular mechanisms remain poorly understood .…”

Section: Introductionmentioning

confidence: 99%

“…9,10 In addition, curcumin can change the properties of cell membranes and hence indirectly effect the membrane proteins. Experimental studies have revealed that curcumin can localize in the membrane, 9,11 increases the membrane permeability, 12,13 induces membrane thinning effect on a concentration dependent manner, 10 and leads to apoptosis-like reversible changes in plasma membrane asymmetry. 12 In spite of curcumin's known membrane activity, the details of molecular mechanisms remain poorly understood.…”

Section: ■ Introductionmentioning

confidence: 99%

Understanding Interactions of Curcumin with Lipid Bilayers: A Coarse-Grained Molecular Dynamics Study

Ileri-Ercan

2019

J. Chem. Inf. Model.

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The interactions of curcumin with various lipid bilayers (POPC, DOPC, oxidized POPC, and oxidized DOPC) and model biomembranes (symmetric bacteria and yeast plasma membranes, as well as asymmetric mammalian plasma membrane) are investigated. A nonlinear thinning effect of curcumin with respect to its concentration is demonstrated in PC membranes and in the yeast. Curcumin induces asymmetry to the symmetric yeast membranes but reduces the degree of asymmetry of the mammalian plasma membranes when the molecule is placed facing the outer leaflets. The molecule is found to diffuse through oxidized PC bilayers, POPC bilayers at a curcumin to lipid ratio C/L = 1/ 5, yeast membranes at C/L = 1/100, and the mammalian plasma membranes at C/L = 1/5 and when the molecule placed facing the outer leaflets. The results of this work demonstrate that the lipid type, the lipid distribution, and curcumin amount play a critical role in defining the interactions of curcumin with the lipids and their transport behavior through the bilayers.

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Cardiolipin mediates curcumin interactions with mitochondrial membranes

Cited by 12 publications

References 41 publications

Curcumin and Carnosic Acid Cooperate to Inhibit Proliferation and Alter Mitochondrial Function of Metastatic Prostate Cancer Cells

Curcumin and Carnosic Acid Cooperate to Inhibit Proliferation and Alter Mitochondrial Function of Metastatic Prostate Cancer Cells

The Cytoprotective Role of Antioxidants in Mammalian Cells Under Rapidly Varying UV Conditions During Stratospheric Balloon Campaign

Understanding Interactions of Curcumin with Lipid Bilayers: A Coarse-Grained Molecular Dynamics Study

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