Arachidonic Acid Enhances Caffeine-Induced Cell Death via Caspase-Independent Cell Death

Kuwayama, Hidekazu

doi:10.1038/srep00577

Cited by 8 publications

(5 citation statements)

References 24 publications

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“…On the other hand, caffeine had no effect on HUVECs differentiation on Matrigel or migration in vitro (data not shown). These results indicate that inhibitory effect of caffeine on angiogenesis is related, at least in part, to its apoptotic effect [50, 51]. …”

Section: Discussionmentioning

confidence: 99%

Caffeine-induced endothelial cell death and the inhibition of angiogenesis

Jin

Son

et al. 2013

Anat Cell Biol

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Numerous studies have shown that adenosine or adenosine agonists can stimulate angiogenesis. However, the effect of caffeine (a known adenosine receptor antagonist) on angiogenesis has not been previously studied. Accordingly, this study was undertaken to examine the effect of caffeine on angiogenesis and to clarify the mechanism involved. Chick chorioallantoic membrane assays were used to investigate the effect of caffeine on angiogenesis and proliferation assays using human umbilical vein endothelial cells (HUVECs), were used to study its effects on specific aspects of angiogenesis. The expressions of caspase-3 and Bcl-2 were examined by western blotting, immunofluorescence staining was used to identify HUVEC morphological changes, and fluorescence activated cell sorting (FACS) and DAPI staining were used to detect HUVEC apoptosis. Caffeine was found to inhibit blood vessel formation dose-dependently and to inhibit the proliferation of HUVECs time- and dose-dependently. FACS analysis and DAPI staining showed that inhibitory effect of caffeine on HUVEC proliferation was the result of apoptosis and the up-regulation of thrombospondin-1 (TSP-1). Furthermore, TSP-1 levels were down-regulated by NECA but were unaffected by CGS21680, indicating that caffeine regulated TSP-1 expression via adenosine A2B receptor. In addition, caffeine up-regulated caspase-3 and down-regulated Bcl-2 at the protein level. These results suggest that the inhibitory effect of caffeine on angiogenesis is associated, at least in part, with its induction of endothelial cell apoptosis, probably mediated by a caspase-3 dependent mechanism.

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Section: Discussionmentioning

confidence: 99%

Caffeine-induced endothelial cell death and the inhibition of angiogenesis

Jin

Son

et al. 2013

Anat Cell Biol

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“…Caffeine inhibits all adenylyl cyclases, viz., ACA, ACB, and ACG in Dictyostelium , and although the exact molecular mechanism of action remains unclear, this inhibition is neither due to ceasing of the secretion of the cAMP produced nor due to hyperactivation of cAMP phosphodiesterases [17] . We found here that the Dd Rbg-3 -null mutant exhibited a caffeine-resistant phenotype and was capable of producing cAMP under a physiologically effective caffeine concentration like cells lacking phospholipase A2 gene [27] , indicating that caffeine acts on adenylyl cyclase via Dd Rbg-3. Although we have yet to determine whether caffeine acts directly on Dd Rbg-3 or via other components, our results indicate that Dd Rbg-3 is involved in the caffeine-mediated inhibition of adenylyl cyclase activity.…”

Section: Discussionmentioning

confidence: 73%

A RabGAP Regulates Life-Cycle Duration via Trimeric G-protein Cascades in Dictyostelium discoideum

et al. 2013

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BackgroundThe life-cycle of cellular slime molds comprises chronobiologically regulated processes. During the growth phase, the amoeboid cells proliferate at a definite rate. Upon starvation, they synthesize cAMP as both first and second messengers in signalling pathways and form aggregates, migrating slugs, and fruiting bodies, consisting of spores and stalk cells, within 24 h. In Dictyostelium discoideum, because most growth-specific events cease during development, proliferative and heterochronic mutations are not considered to be interrelated and no genetic factor governing the entire life-cycle duration has ever been identified.Methodology/Principal FindingsUsing yeast 2-hybrid library screening, we isolated a Dictyostelium discoideum RabGAP, Dd Rbg-3, as a candidate molecule by which the Dictyostelium Gα2 subunit directs its effects. Rab GTPase-activating protein, RabGAP, acts as a negative regulator of Rab small GTPases, which orchestrate the intracellular membrane trafficking involved in cell proliferation. Deletion mutants of Dd rbg-3 exhibited an increased growth rate and a shortened developmental period, while an overexpression mutant demonstrated the opposite effects. We also show that Dd Rbg-3 interacts with 2 Gα subunits in an activity-dependent manner in vitro. Furthermore, both human and Caenorhabditis elegans rbg-3 homologs complemented the Dd rbg-3–deletion phenotype in D. discoideum, indicating that similar pathways may be generally conserved in multicellular organisms.Conclusions/SignificanceOur findings suggest that Dd Rbg-3 acts as a key element regulating the duration of D. discoideum life-span potentially via trimeric G-protein cascades.

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“…This could be due to the presence of caffeine in the Arabica coffee extract. In a study that used mammalian cell line (CHO), caffeine has been found to exhibit acute cellular toxicity by inhibiting the growth and causing death to the cells (Kuwayama, 2012). In vivo study on the acute toxicity of caffeine was reported in animals such as fish (Leuciscus idus) with LC50 of 87 µg/mL after 96 h exposure, rats with LD50 of 200 -400 mg/kg, and mice with LD50 of 185 mg/kg (CCOHS, 2012).…”

Section: Discussionmentioning

confidence: 99%

Comparative nutritional and toxicity analyses of beverages from date seed and barley powders as caffeine-free coffee alternatives

Jamil¹,

Al‐Obaidi²,

Saleh³

et al. 2022

IFRJ

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Coffee is one of the most preferred beverages due to its flavour and aroma, which is partially contributed by the presence of caffeine. However, there are many negative effects of caffeine on human health. Alternative products like date seed and barley beverage have become an interest to switch from caffeine to caffeine-free beverages. The present work thus aimed to evaluate the nutritional properties and toxicity of date seed and barley powders as compared to Arabica coffee powder. Samples were analysed for its caffeine content, antioxidant activity, and toxicity activity from boiled water extract, whereas the nutrition compositions and heavy metal contents were analysed based on respective extraction method performed. A mass spectral peak of caffeine was detected in the Arabica coffee but not in the date seed and barley powders. All three samples were shown to possess antioxidant activities with Arabica coffee yielding the highest. Arabica coffee, however, exhibited a moderate level of toxicity to human lung fibroblast (MRC-5) cell line with IC50 of 230 ± 40 µg/mL at the extract concentration. There was no inhibition on 50% MRC-5 cell viability showed by the date seed and barley powders up to 10 mg/mL extract concentration. The abundance of heavy metals detected in all samples was lower than the regulatory limits. Our findings therefore further supported the advantages of date seed and barley powders as alternatives to coffee beverage as both contained undetected amount of caffeine, low fat and high carbohydrate contents, and possessed good antioxidant activity with low potential health risks.

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Arachidonic Acid Enhances Caffeine-Induced Cell Death via Caspase-Independent Cell Death

Cited by 8 publications

References 24 publications

Caffeine-induced endothelial cell death and the inhibition of angiogenesis

Caffeine-induced endothelial cell death and the inhibition of angiogenesis

A RabGAP Regulates Life-Cycle Duration via Trimeric G-protein Cascades in Dictyostelium discoideum

Comparative nutritional and toxicity analyses of beverages from date seed and barley powders as caffeine-free coffee alternatives

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