Triggering of Erythrocyte Cell Membrane Scrambling by Ursolic Acid

Jilani, Kashif; Abed, Majed; Zelenak, Christine; Lang, Elisabeth; Qadri, Syed M.; Läng, Florian

doi:10.1021/np2005133

Cited by 20 publications

(10 citation statements)

References 49 publications

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“…Bromophycolide S (108) also showed submicromolar activity against the human malaria parasite P. falciparum in comparison to others [58]. It may be helpful in combating malarial parasite as they thrive on erythrocytes [62]. Corallolide A (112) and corallolide B (113) isolated from Carrabean gorgonian octoral Pseudopterogorgia bipinnata were shown to have antiparasitic and antitubercular activity [59].…”

Section: Terpenesmentioning

confidence: 99%

“…, beilschmieflavonoid A (61), and beilschmieflavonoid B(62) showed antibacterial activity against three strains of bacteria, Pseudomonas agarici, Bacillus subtilis, and Streptococcus minor, and antiplasmodial activity against P. falciparum, chloroquine-resistant strain W2[37]. Cyclolignene derivatives from Pycnanthus angolensis roots, namely isolated from antibacterial leaves extract of Melaleuca ericifolia[40].…”

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confidence: 99%

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Recent Developments in Natural Product-Based Drug Discovery in Tropical Diseases

Lal¹,

Singh²

2016

Studies in Natural Products Chemistry

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Section: Terpenesmentioning

confidence: 99%

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confidence: 99%

Recent Developments in Natural Product-Based Drug Discovery in Tropical Diseases

Lal¹,

Singh²

2016

Studies in Natural Products Chemistry

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“…Triggers of eryptosis may include increase of cytosolic Ca 2+ activity ([Ca 2+ ] i ) [34], formation of ceramide [35], energy depletion [34], activated caspases [36,37,38,39,40], activation of casein kinase 1α [41,42], Janus-activated kinase JAK3 [43], protein kinase C [44], or p38 kinase [45], as well as impaired activity of AMP activated kinase AMPK [46], cGMP-dependent protein kinase [37], PAK2 kinase [47], sorafenib sensitive kinases [48], and sunitinib sensitive kinases [49]. Moreover, eryptosis is stimulated by a wide variety of xenobiotics [35,49,50,51,52,53,54,55,56,57,58,59,60,61,62,63,64,65,66,67,68,69,70,71,72,73,74,75,76,77,78,79] including several natural substances [34] including gambogic acid [80], tannic acid [81], ipratropium [82], withaferin [83], tanshinone [58], thymoquinone [84], ursolic acid [85], honokiol [86], saponin [87], apigenin [88], oridonin [89], and alpha-lipoic acid [36]. …”

Section: Introductionmentioning

confidence: 99%

Stimulation of Suicidal Erythrocyte Death by Artesunate

Alzoubi

Calabrò

Bissinger

et al. 2014

Cell Physiol Biochem

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Background: The artemisinin derivative artesunate is effective in the treatment of severe malaria and is considered for the treatment of malignancy. Artesunate triggers tumor cell apoptosis, an effect at least in part mediated by mitochondria. Even though lacking mitochondria, erythrocytes may similarly enter suicidal death or eryptosis, which is characterized by cell shrinkage and breakdown of the phospholipid asymmetry of the cell membrane with phosphatidylserine translocation to the erythrocyte surface. Triggers of eryptosis include increase of cytosolic Ca²⁺-activity ([Ca²⁺]_i), ceramide formation, and oxidative stress. The present study explored whether artesunate stimulates eryptosis. Methods: Phosphatidylserine exposure at the cell surface was estimated from annexin V binding, cell volume from forward scatter, [Ca²⁺]_i from Fluo3-fluorescence, ceramide abundance from binding of specific antibodies, and oxidative stress from 2′,7′-dichlorodihydrofluorescein-diacetate fluorescence. Results: A 48 h exposure of human erythrocytes to artesunate significantly increased the percentage of annexin-V-binding cells (≥ 9 µg/ml) without significantly influencing forward scatter. Artesunate significantly increased [Ca²⁺]_i. The stimulation of annexin-V-binding by artesunate (15 µg/ml) was significantly blunted but not abolished by removal of extracellular Ca²⁺. Artesunate increased the ceramide abundance at the cell surface and the 2′,7′-dichlorodihydrofluorescein-diacetate fluorescence. Conclusions: Artesunate stimulates phosphatidylserine translocation at the erythrocyte cell membrane, an effect at least partially due to increase of [Ca²⁺]_i, stimulation of ceramide formation and generation of oxidative stress.

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“…Eryptosis is further stimulated by activated caspases and deranged activities of AMP‐activated kinase (AMPK) , casein kinase 1α , cGMP‐dependent protein kinase , Janus‐activated kinase (JAK) 3 , protein kinase C , p38 kinase , PAK2 kinase , sorafenib‐sensitive kinases and sunitinib‐sensitive kinases . Eryptosis could further be triggered by a wide variety of xenobiotics including the natural substances apigenin , alpha‐lipoic acid , curcumin , gambogic acid , honokiol , ipratropium , oridonin , saponin , tannic acid , tanshinone , thymoquinone , ursolic acid and withaferin .…”

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confidence: 99%

Stimulation of Suicidal Erythrocyte Death by Ellipticine

Calabrò

Alzoubi

Bissinger

et al. 2014

Basic Clin Pharma Tox

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Ellipticine is a potent antineoplastic alkaloid effective in part by triggering apoptosis. Mechanisms involved in ellipticine-induced apoptosis include mitochondrial depolarization and DNA damage. Erythrocytes lack mitochondria and nuclei but may nevertheless enter suicidal death or eryptosis, which is characterized by cell shrinkage and phosphatidylserine translocation to the erythrocyte surface. Stimulators of eryptosis include increase in cytosolic Ca 2+ activity ([Ca 2+ ] i ), ceramide formation and oxidative stress. This study tested whether ellipticine stimulates eryptosis. Phosphatidylserine exposure at the cell surface was estimated from annexin V binding, cell volume from forward scatter (FSC), [Ca 2+ ] i from Fluo-3 fluorescence, ceramide abundance from binding of specific antibodies and reactive oxygen species from 2 0 ,7 0 -dichlorodihydrofluorescein diacetate fluorescence. A 24-hr exposure of human erythrocytes to ellipticine (5 lg/ml) significantly increased the percentage of annexin V binding cells, ceramide abundance and oxidative stress. Ellipticine did not significantly modify [Ca 2+ ] i , and the stimulation of annexin V binding by ellipticine (5 lg/ml) did not require the presence of extracellular Ca 2+ . Ellipticine (5 lg/ml) did not significantly modify FSC. Ionomycin (1 lM, 1 hr) decreased FSC, an effect slightly but significantly blunted by ellipticine (5 lg/ml). Ellipticine thus stimulates phosphatidylserine translocation in the erythrocyte cell membrane, an effect at least partially due to stimulation of oxidative stress and ceramide formation.Ellipticine, an anticancer alkaloid [1], is a powerful stimulator of tumour cell apoptosis [2][3][4][5][6][7][8][9]. The substance is in part effective by inducing oxidative stress [4], translocation of p53 into nuclei [10,11] and mitochondria [12], mitochondrial depolarization with the release of cytochrome c and apoptosis-inducing factor [4][5][6][7] as well as caspase activation [4,7]. Ellipticine induces oxidative DNA damage [9] with DNA intercalation, inhibition of topoisomerase II and formation of covalent DNA adducts [1,[13][14][15]. The apoptotic effect of ellipticine is reversed by the lipophilic antioxidant a-tocopherol [9].Human erythrocytes lack mitochondria and nuclei [16] but may nevertheless enter an apoptosis-like suicidal cell death or eryptosis, which is characterized by cell shrinkage and cell membrane scrambling with translocation of phosphatidylserine from the inner cell membrane leaflet to the cell surface [16] This study explored whether ellipticine is able to induce eryptosis. To this end, human erythrocytes from healthy individuals have been exposed to ellipticine and phosphatidylserine surface abundance, cell volume, [Ca 2+ ] i , ceramide and oxidative stress quantified by flow cytometry. Materials and MethodsErythrocytes, solutions and chemicals. Fresh Li-Heparinanticoagulated blood samples were kindly provided by the blood bank of the University of T€ ubingen. The study was approved by the Ethics Committee ...

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Triggering of Erythrocyte Cell Membrane Scrambling by Ursolic Acid

Cited by 20 publications

References 49 publications

Recent Developments in Natural Product-Based Drug Discovery in Tropical Diseases

Recent Developments in Natural Product-Based Drug Discovery in Tropical Diseases

Stimulation of Suicidal Erythrocyte Death by Artesunate

Stimulation of Suicidal Erythrocyte Death by Ellipticine

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