75 research outputs found
Nanoencapsulation of dietary flavonoid fisetin: Formulation and in vitro antioxidant and α-glucosidase inhibition activities
No full textThe bioactive flavonoid fisetin (FS) is a diet-derived antioxidant that is being increasingly investigated for its health-promoting effects. Unfortunately, the poor physicochemical and pharmacokinetic properties affect and limit the clinical application. In this study, novel polymeric nanoparticles (NPs), based on Poly-(ε-caprolactone) (PCL) and PLGA-PEG-COOH, encapsulating FS were formulated as suitable oral controlled release systems. Results showed NPs having a mean diameter of 140-200 nm, and a percent loading of FS ranging from 70 to 82%. In vitro release studies revealed that NPs are able to protect and preserve the release of FS in gastric simulated conditions, also controlling the release in the intestinal medium. Moreover, the DPPH and ABTS scavenging capacity of FS, as well as α-glucosidase inhibition activity, that resulted about 20-fold higher than commercial Acarbose, were retained during nanoencapsulation process. In summary, our developed NPs can be proposed as an attractive delivery system to control the release of antioxidant and anti-hyperglycemic FS for nutraceutical and/or therapeutic application
Fisetin inhibits human melanoma cell growth through direct binding to p70S6K and mTOR: findings from 3-D melanoma skin equivalents and computational modeling.
No full textPomegranate juice consumption reduces simulated ischemic stroke damage and increases brain antioxidant status in rats
No full textPomegranate phytochemicals / Navindra P. Seeram ... [et al.] -- Antioxidative properties of pomegranate : in vitro studies / Mira Rosenblat and Michael Aviram -- Bioavailability of pomegranate polyphenols / Francisco A. Tom?s-Barber?n, Navindra P. Seeram, and Juan Carlos Esp?n -- Protection against cardiovascular disease / Bianca Fuhrman and Michael Aviram -- Protection against stroke / Marva I. Sweeney-Nixon -- Anticancer potential of pomegranate / Shishir Shishodia ... [et al.] -- Molecular mechanisms of chemoprevention of cancer by pomegranate / Deeba Syed ... [et al.] -- Pomegranate and prostate cancer chemoprevention / John T. Leppert and Allan J. Pantuck -- Assessment of estrogenicity of pomegranate in an in vitro bioassay / Diane M. Harris, Emily Besselink, and Navindra P. Seeram -- Absence of significant estrogenic effects in the postmenopausal population / Michelle P. Warren ... [et al.] -- Antimicrobial activities of pomegranate / G.K. Jayaprakasha, P.S. Negi, B.S. Jena -- Commercialization of pomegranates : fresh fruit, beverages, and botanical extracts / Navindra P. Seeram, Yanjun Zhang, and David Heber -- Pomegranates: a botanical perspective / David W. Still -- Postharvest biology and technology of pomegranates / Adel A. Kader
Role of YB-1, a regulator of epithelial to mesenchymal transition, in prostate cancer: Inhibition by a dietary flavonoid fisetin
No full textFisetin targets YB-1/RSK axis independent of its effect on ERK signaling: insights from in vitro and in vivo melanoma models
No full textAbstract The anti-proliferative activity of dietary flavonoid fisetin has been validated in various cancer models. Establishing its precise mechanism of action has proved somewhat challenging given the multiplicity of its targets. We demonstrated that YB-1 promotes epithelial-to-mesenchymal transition and its inhibition suppressed tumor cell proliferation and invasion. The p90 ribosomal S6 kinase (RSK), an important ERK effector, activates YB-1 to drive melanoma growth. We found that fisetin treatment of monolayer/3-D melanoma cultures resulted in YB-1 dephosphorylation and reduced transcript levels. In parallel, fisetin suppressed mesenchymal markers and matrix-metalloproteinases in melanoma cells. Data from cell-free/cell-based systems indicated that fisetin inhibited RSK activity through binding to the kinase. Affinity studies for RSK isoforms evaluated stronger interaction for RSK2 than RSK1. Competition assays performed to monitor binding responses revealed that YB-1 and RSK2 do not compete, rather binding of fisetin to RSK2 promotes its binding to YB-1. Fisetin suppressed YB-1/RSK signaling independent of its effect on ERK, and reduced MDR1 levels. Comparable efficacy of fisetin and vemurafenib for inhibiting melanoma growth was noted albeit through divergent modulation of ERK. Our studies provide insight into additional modes of regulation through which fisetin interferes with melanoma growth underscoring its potential therapeutic efficacy in disease progression
Abstract 1179: Unique metabolic profile of Vemurafenib-resistant melanoma cells: a quantitative proteomics approach
No full textAbstract:
Malignant melanoma is noted for its aggressive clinical behavior and propensity for lethal metastasis. Despite the remarkable success of BRAF inhibitor Vemurafenib in clinics, emergence of resistance remains a limiting factor in increasing overall survival. Thus, comprehensive studies are needed to increase the biological understanding of BRAF-resistant tumors in order to develop effective therapeutic regimens. To study the molecular mechanism(s) involved in acquired resistance, we generated a Vemurafenib-resistant cell line in the BRAFV600E mutated SK-Mel28 melanoma cell background. Incubation of SK-Mel28 cells with Vemurafenib (0.1 μM) resulted in an initial loss of cell viability after which majority of cells resumed proliferation. Thereafter, cells were exposed to gradually increasing Vemurafenib concentrations and allowed to proliferate in the presence of 5 μM Vemurafenib, to generate the A2-1b resistant cell line. Viability assays established the IC50 of parental SK-Mel28 cells as 0.2 μM, while IC50 > than 12 μM was noted for the Vemurafenib-resistant A2-1b population. We utilized a quantitative proteomics strategy, employing label-free nano-LC-MS/MS technology on a Q-exactive, to compare the proteome of A2-1b with SK-Mel28 cells. The data searched against the human proteome using the Sequest search engine and further analyzed with SIEVE software resulted in the positive identification of 1720 proteins (≤1% FDR). This data set containing proteins with only uniquely identified peptides with a high level of confidence (p<0.05) was uploaded into Ingenuity Pathway Analysis and Panther softwares, with number of peptides and corresponding ratio between the two groups, set as observational parameters. Notably, the largest fraction (49%) of identified proteins belonged to cellular metabolic processes. Glycolysis, gluconeogenesis and NADH repair were the major pathways modulated in Vemurafenib-resistant A2-1b cells. In addition, TCA cycle and unfolded protein response was significantly affected. A subset of 13 proteins, linked to these pathways and not previously associated with acquired resistance was identified. The upregulated proteins included CALD1, OR4A15, PTPRK, CALU, IDH3A, RNH1, CLIC4, SPAG17, SND1 and VCP while ENO2, TPI1 and GAPDH were significantly downregulated. In summary, the proteomic approach applied for the first time to study acquired resistance to BRAF inhibition identified novel targets which upon further validation in appropriate models has the potential to provide valuable therapeutic strategies against Vemurafenib-resistant melanomas.
Citation Format: Deeba N. Syed, Rahul K. Lall, Iram Majeed, Feng Liu, Frank L. Meyskens, Hasan Mukhtar. Unique metabolic profile of Vemurafenib-resistant melanoma cells: a quantitative proteomics approach. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 1179. doi:10.1158/1538-7445.AM2015-117
Gender Bias in Skin Cancer: Role of Catalase Revealed
No full textSullivan et al. describe their finding that lower skin catalase activity in male as compared with female mice may be responsible for the increased skin carcinogenesis observed in UVB radiation–exposed male mice. This adds to the growing literature that points toward a gender bias in the pathogenesis of skin cancer. Delineating the events between UV exposure and carcinogenesis in relation to skin’s antioxidant activity will provide insight into disease progression, prognosis, and responses to therapy. If substantiated with further studies in humans, this information may aid in designing gender-specific preventive measures aimed at reversing immune suppression through targeting the altered redox status in UV-exposed individuals
FICZ: A Messenger of Light in Human Skin
No full textPhotosensitization, subsequent to photon absorption by chromophores present in the human skin, appears to be a key mechanism of UV-induced oxidative stress. The tryptophan photoproduct 6-formylindolo[3,2-b]carbazole (FICZ), an aryl hydrocarbon receptor ligand, has been found to be a potent UVA photosensitizer, effective at nanomolar concentrations. A novel addition to the family of endogenous photosensitizers, the precise mechanism(s) through which it mediates oxidative stress in UVA exposed skin and its response to the UVB spectrum of the solar UV flux remains unexplored. Further studies related to its functionality in the human skin, its utility as a tool against UV-induced adverse effects, and its role in inflammatory skin diseases will have the potential to open up new avenues in the realms of human skin photobiology
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