scholarly journals Fucoxanthin, A Carotenoid Derived from Phaeodactylum tricornutum Exerts Antiproliferative and Antioxidant Activities In Vitro

Antioxidants ◽  
2019 ◽  
Vol 8 (6) ◽  
pp. 183 ◽  
Author(s):  
Ulrike Neumann ◽  
Felix Derwenskus ◽  
Verena Flaiz Flister ◽  
Ulrike Schmid-Staiger ◽  
Thomas Hirth ◽  
...  

Microalgae contain a multitude of nutrients and can be grown sustainably. Fucoxanthin, a carotenoid from Phaeodactylum tricornutum, could have beneficial health effects. Therefore, we investigated the anti-inflammatory, antioxidative and antiproliferative effects of fucoxanthin derived from this diatom in vitro. The effects of purified fucoxanthin on metabolic activity were assessed in blood mononuclear cells and different cell lines. In cell lines, caspase 3/7 activity was also analyzed. Nitrogen monoxide release and mRNA-expression of proinflammatory cytokines were measured. For antioxidant assays, cell free assays were conducted. Additionally, the antioxidant effect in neutrophils was quantified and glutathione was determined in HeLa cells. The results show that neither did fucoxanthin have anti-inflammatory properties nor did it exert cytotoxic effects on mononuclear cells. However, the metabolic activity of cell lines was decreased up to 58% and fucoxanthin increased the caspase 3/7 activity up to 4.6-fold. Additionally, dose-dependent antioxidant effects were detected, resulting in a 63% decrease in chemiluminescence in blood neutrophils and a 3.3-fold increase in the ratio of reduced to oxidized glutathione. Our studies show that fucoxanthin possesses antiproliferative and antioxidant activities in vitro. Hence, this carotenoid or the whole microalgae P. tricornutum could be considered as a food or nutraceutical in human nutrition, showcasing beneficial health effects.

Blood ◽  
1998 ◽  
Vol 92 (10) ◽  
pp. 3804-3816 ◽  
Author(s):  
John C. Byrd ◽  
Charlotte Shinn ◽  
Jamie K. Waselenko ◽  
Ephraim J. Fuchs ◽  
Teresa A. Lehman ◽  
...  

Abstract Flavopiridol has been reported to induce apoptosis in lymphoid cell lines via downregulation of bcl-2. The in vitro activity of flavopiridol against human chronic lymphocytic leukemia (CLL) cells and potential mechanisms of action for inducing cytotoxicity were studied. The in vitro viability of mononuclear cells from CLL patients (n = 11) was reduced by 50% at 4 hours, 24 hours, and 4 days at a flavopiridol concentration of 1.15 μmol/L (95% confidence interval [CI] ±0.31), 0.18 μmol/L (95% CI ±0.04), and 0.16 μmol/L (95% CI ±0.04), respectively. Loss of viability in human CLL cells correlated with early induction of apoptosis. Exposure of CLL cells to 0.18 μmol/L of flavopiridol resulted in both decreased expression of p53 protein and cleavage of the caspase-3 zymogen 32-kD protein with the appearance of its 20-kD subunit. Contrasting observations of others in tumor cell lines, flavopiridol cytotoxicity in CLL cells did not correlate with changes in bcl-2 protein expression alterations. We evaluated flavopiridol’s dependence on intact p53 by exposing splenocytes from wild-type (p53+/+) and p53 null (p53−/−) mice that demonstrated no preferential cytotoxicity as compared with a marked differential with F-ara-a and radiation. Incubation of CLL cells with antiapoptotic cytokine interleukin-4 (IL-4) did not alter the LC50 of flavopiridol, as compared with a marked elevation noted with F-ara-a in the majority of patients tested. These data demonstrate that flavopiridol has significant in vitro activity against human CLL cells through activation of caspase-3, which appears to occur independently of bcl-2 modulation, the presence of IL-4, or p53 status. Such findings strongly support the early introduction of flavopiridol into clinical trials for patients with B-CLL.


Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 2473-2473
Author(s):  
O. Giles Best ◽  
Stephen P Mulligan

Abstract Abstract 2473 Introduction: Resistance to fludarabine-based treatment represents a challenge in the clinical management of Chronic Lymphocytic Leukemia (CLL). Despite the unprecedented response rates seen with the fludarabine (F), cyclophosphamide (C), Rituximab (R) regimen novel treatment strategies are required that do not rely on an intact p53 signaling pathway. We recently described the activity of a novel, synthetic inhibitor of the molecular chaperone, heat-shock protein 90 (Hsp90) named SNX7081 (Serenex, now Pfizer) against CLL cells in vitro (Best et al., 2010 BJH). Here we explored the effect of this inhibitor on the fludarabine sensitivity of 3 haematological cell lines and 12 patient samples with mutations of ATM or TP53. Methods: Mononuclear cells were isolated by density centrifugation from CLL patients following informed consent. The 13 patient samples selected for study were determined to have mutations of either ATM or TP53 using a functional assay described in detail elsewhere (Best et al., 2008). The Mec1 (CLL), Mec2 (CLL) and U266 (B-ALL) cell lines were maintained under standard conditions in RPMI-1640 with 2mM L-glut and 1% pen/strep. Sensitivity to fludarabine, with and without SNX7081, was assessed using the MTT (3–4, 5-dimethylthiazol-2,5-diphenyl tetrazolium bromide) assay. Synergy between the agents, activation of caspase-3 and the induction of double stranded DNA (dsDNA) breaks following treatment were all assessed by flow cytometry using the mitochondrial membrane potential dye DilC1 (5) and propidium iodide (PI) or appropriate antibodies. Results: The IC50 for fludarabine was significantly higher in the 3 cell lines and 13 patient samples with ATM/TP53 lesions than in 4 cell lines or 10 patient samples defined as ATM/TP53 wild-type. Simultaneous exposure to a combination of fludarabine and SNX7081 at a ratio based on the IC50 of the compounds as single agent significantly reduced the IC50 for fludarabine (P<0.01); in 11 patient samples the IC50 for fludarabine was reduced to within a clinically achievable range (<5μM). Synergy between fludarabine and SNX7081 was evident as an effect on the distribution of the cell lines in the cell cycle and as a marked effect on the proportion of apoptotic cells (DilC (1)5 negative/PI negative) in cultures of both the cell lines and patient samples. Furthermore, we show that the combination of the compounds has a greater than additive effect on the activation of caspase-3 and on the formation of dsDNA breaks, as evidenced by the phosphorylation of g-H2Ax. Conclusions: Our studies suggest that inhibition of Hsp90 may overcome fludarabine resistance conferred by mutations of ATM or TP53. The mechanism of the synergy between these compounds appears to be via augmentation of fludarabine-induced dsDNA breaks and is concomitant with an increase in caspase-3 signaling. The data suggest that this combination may represent a promising regimen in the treatment of fludarabine-refractory CLL. Disclosures: Mulligan: Roche: Honoraria, Membership on an entity's Board of Directors or advisory committees; Bayer Schering, now Genzyme: Honoraria.


Blood ◽  
1998 ◽  
Vol 92 (10) ◽  
pp. 3804-3816 ◽  
Author(s):  
John C. Byrd ◽  
Charlotte Shinn ◽  
Jamie K. Waselenko ◽  
Ephraim J. Fuchs ◽  
Teresa A. Lehman ◽  
...  

Flavopiridol has been reported to induce apoptosis in lymphoid cell lines via downregulation of bcl-2. The in vitro activity of flavopiridol against human chronic lymphocytic leukemia (CLL) cells and potential mechanisms of action for inducing cytotoxicity were studied. The in vitro viability of mononuclear cells from CLL patients (n = 11) was reduced by 50% at 4 hours, 24 hours, and 4 days at a flavopiridol concentration of 1.15 μmol/L (95% confidence interval [CI] ±0.31), 0.18 μmol/L (95% CI ±0.04), and 0.16 μmol/L (95% CI ±0.04), respectively. Loss of viability in human CLL cells correlated with early induction of apoptosis. Exposure of CLL cells to 0.18 μmol/L of flavopiridol resulted in both decreased expression of p53 protein and cleavage of the caspase-3 zymogen 32-kD protein with the appearance of its 20-kD subunit. Contrasting observations of others in tumor cell lines, flavopiridol cytotoxicity in CLL cells did not correlate with changes in bcl-2 protein expression alterations. We evaluated flavopiridol’s dependence on intact p53 by exposing splenocytes from wild-type (p53+/+) and p53 null (p53−/−) mice that demonstrated no preferential cytotoxicity as compared with a marked differential with F-ara-a and radiation. Incubation of CLL cells with antiapoptotic cytokine interleukin-4 (IL-4) did not alter the LC50 of flavopiridol, as compared with a marked elevation noted with F-ara-a in the majority of patients tested. These data demonstrate that flavopiridol has significant in vitro activity against human CLL cells through activation of caspase-3, which appears to occur independently of bcl-2 modulation, the presence of IL-4, or p53 status. Such findings strongly support the early introduction of flavopiridol into clinical trials for patients with B-CLL.


Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 4681-4681
Author(s):  
Veena S. Fauble ◽  
Catherine Lobocki ◽  
Amy Eapen ◽  
Howard R. Terebelo

Abstract Bortezomib (PS341, Velcade) is a selective, reversible proteosome inhibitor. It is a unique inhibitor of the ubiquitin-proteosome pathway leading to arrest in tumor growth, induction of apoptosis, inhibition of tumor metastasis and angiogenesis. It plays an important role in the activation of NF Kappa B, which is responsible for transcription of inhibitors in apoptosis. It is a novel therapeutic agent that has demonstrated in vitro and in vivo activity in mantle cell lymphoma (MCL). In one phase II study, O’Conner et al reported that bortezomib demonstrated a response rate of 50% in refractory cases of mantle cell lymphoma, where as in small lymphocytic lymphoma there was a 0% response rate. Why certain types of non-Hodgkins lymphoma (NHL) are sensitive to this agent and others resistant is currently not well understood. It is believed that disregulation has been shown to play a role in the development of drug resistance in NHL Our objective was to determine the efficacy of bortezomib in vitro using three subtypes of NHL. Three lymphocytic cell lines were used: Granta-519 (mantle cell lymphoma), Toledo (diffuse large cell lymphoma) and EHEB (chronic B cell leukemia). The cytotoxic effects were determined by the colorimetric MTT assay after 24 hours of treatment with bortezomib (1 – 20 nM). Apoptosis was assessed by measuring Caspase-3 activity after 6 and 16 hours of treatment with bortezomib (4 or 20 nM). Bortezomib demonstrated a dose-dependent cytotoxic effect for all three cell lines, with an IC50 of 3.5 nM, 4.1 nM, and 18.5 nM for Toledo, Granta-519 and EHEB, respectively. Apoptotic studies showed that bortezomib (20 nM) induced a 1.4 to 5.6-fold increase (after 6 hrs) and 5.8 to 16.6-fold increase (after 16 hrs) in apoptosis. The EHEB cell line was most resistant, showing no increase in Caspase-3 activity at the lower dose (4 nM) at either time-point. Granta-519 was most sensitive showing a 5.2-fold increase in apoptosis with the lower dose after 16 hours of treatment. This in vitro study demonstrated a dose and time dependent response of bortezomib in both the mantle cell lymphoma (Granta-519) and the diffuse large cell lymphoma (Toledo) cell lines. The resistance to bortezomib in the chronic B cell leukemia (EHEB) cell line was confirmed in this study as evidenced by the lack of Caspase-3 activity at the 4 nM dose at both 6 and 16 hours. Our future studies will attempt to unmask the reason for this resistance. Perhaps manipulation of the apoptotic pathway through the use of combinations of various biologic response modifiers may be an attractive option in overcoming resistance in certain subtypes of NHL.


Separations ◽  
2021 ◽  
Vol 8 (5) ◽  
pp. 57
Author(s):  
Rokayya Sami ◽  
Abeer Elhakem ◽  
Mona Alharbi ◽  
Manal Almatrafi ◽  
Nada Benajiba ◽  
...  

Onions contain high antioxidants compounds that fight inflammation against many diseases. The purpose was to investigate some selected bioactive activities of onion varieties (Yellow, Red, Green, Leek, and Baby). Antioxidant assays and anti-inflammatory activities such as NO production with the addition of some bioactive components were determined and analyzed by using a spectrophotometer. Gas chromatography and mass spectrometry (GC–MS) was used for the volatile compounds, while an Atomic absorption spectrometer was used for mineral determinations. Red variety achieved the highest antioxidant activities. The total flavonoids were between (12.56 and 353.53 mg Quercetin/gin dry weight) (dw) and the total phenol was (8.75–25.73 mg/g dw). Leek, Yellow and Green extracts achieved highly anti-inflammatory values (3.71–4.01 μg/mL) followed by Red and Baby extracts, respectively. The highest contents of sodium, potassium, zinc, and calcium were established for Red onions. Furfuraldehyde, 5-Methyl-2-furfuraldehyde, 2-Methyl-2-pentenal, and 1-Propanethiol were the most predominant, followed by a minor abundance of the other compounds such as Dimethyl sulfide, Methyl allyl disulfide, Methyl-trans-propenyl-disulfide, and Methyl propyl disulfide. The results recommend that these varieties could act as sources of essential antioxidants and anti-inflammatories to decrease inflammation and oxidative stresses, especially red onions that recorded high activities.


Molecules ◽  
2021 ◽  
Vol 26 (11) ◽  
pp. 3303
Author(s):  
Amina M. G. Zedan ◽  
Mohamed I. Sakran ◽  
Omar Bahattab ◽  
Yousef M. Hawsawi ◽  
Osama Al-Amer ◽  
...  

The use of insects as a feasible and useful natural product resource is a novel and promising option in alternative medicine. Several components from insects and their larvae have been found to inhibit molecular pathways in different stages of cancer. This study aimed to analyze the effect of aqueous and alcoholic extracts of Vespa orientalis larvae on breast cancer MCF7 cells and investigate the underlying mechanisms. Our results showed that individual treatment with 5% aqueous or alcoholic larval extract inhibited MCF7 proliferation but had no cytotoxic effect on normal Vero cells. The anticancer effect was mediated through (1) induction of apoptosis, as indicated by increased expression of apoptotic genes (Bax, caspase3, and p53) and decreased expression of the anti-apoptotic gene Bcl2; (2) suppression of intracellular reactive oxygen species; (3) elevation of antioxidant enzymes (CAT, SOD, and GPx) and upregulation of the antioxidant regulator Nrf2 and its downstream target HO-1; (4) inhibition of migration as revealed by in vitro wound healing assay and downregulation of the migration-related gene MMP9 and upregulation of the anti-migratory gene TIMP1; and (5) downregulation of inflammation-related genes (NFκB and IL8). The aqueous extract exhibited the best anticancer effect with higher antioxidant activities but lower anti-inflammatory properties than the alcoholic extract. HPLC analysis revealed the presence of several flavonoids and phenolic compounds with highest concentrations for resveratrol and naringenin in aqueous extract and rosmarinic acid in alcoholic extract. This is the first report to explain the intracellular pathway by which flavonoids and phenolic compounds-rich extracts of Vespa orientalis larvae could induce MCF7 cell viability loss through the initiation of apoptosis, activation of antioxidants, and inhibition of migration and inflammation. Therefore, these extracts could be used as adjuvants for anticancer drugs and as antioxidant and anti-inflammatory agents.


2021 ◽  
Vol 9 (6) ◽  
pp. 1305
Author(s):  
Carlos Alonso Domínguez-Alemán ◽  
Luis Alberto Sánchez-Vargas ◽  
Karina Guadalupe Hernández-Flores ◽  
Andrea Isabel Torres-Zugaide ◽  
Arturo Reyes-Sandoval ◽  
...  

A common hallmark of dengue infections is the dysfunction of the vascular endothelium induced by different biological mechanisms. In this paper, we studied the role of recombinant NS1 proteins representing the four dengue serotypes, and their role in promoting the expression and release of endocan, which is a highly specific biomarker of endothelial cell activation. We evaluated mRNA expression and the levels of endocan protein in vitro following the stimulation of HUVEC and HMEC-1 cell lines with recombinant NS1 proteins. NS1 proteins increase endocan mRNA expression 48 h post-activation in both endothelial cell lines. Endocan mRNA expression levels were higher in HUVEC and HMEC-1 cells stimulated with NS1 proteins than in non-stimulated cells (p < 0.05). A two-fold to three-fold increase in endocan protein release was observed after the stimulation of HUVECs or HMEC-1 cells with NS1 proteins compared with that in non-stimulated cells (p < 0.05). The blockade of Toll-like receptor 4 (TLR-4) signaling on HMEC-1 cells with an antagonistic antibody prevented NS1-dependent endocan production. Dengue-infected patients showed elevated serum endocan levels (≥30 ng/mL) during early dengue infection. High endocan serum levels were associated with laboratory abnormalities, such as lymphopenia and thrombocytopenia, and are associated with the presence of NS1 in the serum.


Author(s):  
Abhishek Chatterjee ◽  
Dileep Singh Baghel ◽  
Bimlesh Kumar ◽  
Saurabh Singh ◽  
Narendra Kumar Pandey ◽  
...  

Objective: The aims of the present investigation were to develop the herbal and/or herbomineral formulations of Hinguleswara rasa and to compare their anti-inflammatory and antioxidant activities, in vitro, with that of standard drug samples.Methods: This study was an interventional investigation in three samples: In the first sample, Hinguleswara rasa (HR1) was prepared as per methodology described in Rasatarangini using Shuddha Hingula (10 g), Shuddha Vatsanabha (10 g), and Pippali (10 g). In the second and third sample, respectively, Hinguleswara rasa was prepared by replacing Shuddha Hingula with Kajjali where Kajjali made from Hingulotha parada and Sodhita parada constitutes two varieties of Hinguleswara rasa, i.e. HR2 and HR3. In vitro antioxidant activity was studied using 2,2-diphenyl-1-picrylhydrazyl, and the absorbance was recorded at 517 nm. For evaluating the in vitro anti-inflammatory studies, the inhibition of albumin denaturation technique was performed.Results: The results showed that the formulation of Hinguleswara rasa has shown dose-dependent activity which was observed in 100 μg concentration. HR1, HR2, and HR3 showed 36.11, 17.22, and 16.11% radical scavenging activity.Conclusion: It could be concluded that the changes made in the formulations did not affect the in vitro anti-inflammatory and antioxidant effects of the herbomineral formulations.


2014 ◽  
Vol 9 (11) ◽  
pp. 1934578X1400901 ◽  
Author(s):  
Reina M. Toro ◽  
Diana M. Aragón ◽  
Luis F. Ospina ◽  
Freddy A. Ramos ◽  
Leonardo Castellanos

Physalis peruviana calyces are used extensively in folk medicine. The crude ethanolic extract and some fractions of calyces were evaluated in order to explore antioxidant and anti-inflammatory activities. The anti-inflammatory activity was evaluated by the TPA-induced ear edema model. The antioxidant in vitro activity was measured by means of the superoxide and nitric oxide scavenging activity of the extracts and fractions. The butanolic fraction was found to be promising due to its anti-inflammatory and antioxidant activities. Therefore, a bio-assay guided approach was employed to isolate and identify rutin (1) and nicotoflorin (2) from their NMR spectroscopic and MS data. The identification of rutin in calyces of P. peruviana supports the possible use of this waste material for phytotherapeutic, nutraceutical and cosmetic preparations.


2019 ◽  
Vol 25 (37) ◽  
pp. 4946-4967 ◽  
Author(s):  
Anna K. Kiss ◽  
Jakub P. Piwowarski

The popularity of food products and medicinal plant materials containing hydrolysable tannins (HT) is nowadays rapidly increasing. Among various health effects attributable to the products of plant origin rich in gallotannins and/or ellagitannins the most often underlined is the beneficial influence on diseases possessing inflammatory background. Results of clinical, interventional and animal in vivo studies clearly indicate the antiinflammatory potential of HT-containing products, as well as pure ellagitannins and gallotannins. In recent years a great emphasis has been put on the consideration of metabolism and bioavailability of natural products during examination of their biological effects. Conducted in vivo and in vitro studies of polyphenols metabolism put a new light on this issue and indicate the gut microbiota to play a crucial role in the health effects following their oral administration. The aim of the review is to summarize the knowledge about HT-containing products’ phytochemistry and their anti-inflammatory effects together with discussion of the data about observed biological activities with regards to the current concepts on the HTs’ bioavailability and metabolism. Orally administered HT-containing products due to the limited bioavailability of ellagitannins and gallotannins can influence immune response at the level of gastrointestinal tract as well as express modulating effects on the gut microbiota composition. However, due to the chemical changes being a result of their transit through gastrointestinal tract, comprising of hydrolysis and gut microbiota metabolism, the activity of produced metabolites has to be taken into consideration. Studies regarding biological effects of the HTs’ metabolites, in particular urolithins, indicate their strong and structure-dependent anti-inflammatory activities, being observed at the concentrations, which fit the range of their established bioavailability. The impact of HTs on inflammatory processes has been well established on various in vivo and in vitro models, while influence of microbiota metabolites on silencing the immune response gives a new perspective on understanding anti-inflammatory effects attributed to HT containing products, especially their postulated effectiveness in inflammatory bowel diseases (IBD) and cardiovascular diseases.


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