One University Place

West University Place, LA, United States

One University Place

West University Place, LA, United States
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Mahdavian E.,One University Place | Palyok P.,One University Place | Adelmund S.,One University Place | Williams-Hart T.,LSU Shreveport | And 13 more authors.
BMC Research Notes | Year: 2014

Results: Herein, we report that FC101 exhibits very potent in-vitro growth inhibitory effects (IC50ranging from 10nM-2.5 μM) against HaCat (pre-malignant skin), P9-WT (malignant skin), MCF-7 (low malignant breast), MDA-231 (malignant breast), SV-HUC (premalignant bladder), UM-UC14 (malignant bladder), and PC3 (malignant prostate) in a time-course and dose-dependent manner, with the UM-UC14 cells being the most sensitive. FC101 induces apoptosis and an increase in proportion of cells in the sub-G1 phase in both HaCat and P9-WT cell lines as evidenced by cell cycle profile analysis. In a mouse xenograft SCC tumor model, FC101 was well tolerated, non-toxic, and achieved a 30% reduction in tumor size at a dose of 8 mg/kg/day. FC101 is also a potent anti-angiogenenic agent. At nanomolar doses, FC101 inhibits the vascular endothelial growth factor-A (VEGF-A)-mediated proliferation of endothelial cells.Conclusions: Our data presented here indicates that FC101 is an excellent lead candidate for a small molecule anti-cancer agent that simultaneously affects angiogenesis signaling, cancer signal transduction, and apoptosis. Further understanding of the underlying FC101's molecular mechanism may lead to the design of novel targeted and selective therapeutics, both of which are pursued targets in cancer drug discovery.Background: Fusarochromanone (FC101) is a small molecule fungal metabolite with a host of interesting biological functions, including very potent anti-angiogenic and direct anti-cancer activity. © 2014 Mahdavian et al.; licensee BioMed Central Ltd.


Gade W.,One University Place | Gade J.,One University Place | Collins M.,One University Place | Schmit J.,One University Place | Schupp N.,One University Place
Clinical laboratory science : journal of the American Society for Medical Technology | Year: 2010

From hot dogs to Hashimoto's and inheritance to inactivity, many "entrance ramps" converge onto the "Highway to Obesity", each contributing caloric intake that exceeds expenditure. Initially, the hypothalamus regulates appetite and energy based on leptin feedback, until feedback failure increases appetite, and allows deposition of abdominal fat, metabolic dysregulation, and metabolic syndrome. Without feedback controls, progress toward obesity is unimpeded unless diet, exercise, and/or medications provide an exit ramp.


Trutschl M.,One University Place | Kilgore P.C.S.R.,One University Place | Cvek U.,One University Place
Lecture Notes in Computer Science (including subseries Lecture Notes in Artificial Intelligence and Lecture Notes in Bioinformatics) | Year: 2013

Parallel coordinates has shown itself to be a powerful method of exploring and visualizing multidimensional data. However, applying this method to large datasets often introduces clutter, resulting in reduced insight of the data under investigation. We present a new technique that combines the classical parallel coordinates plot with a synthesized dimension that uses topological proximity as an indicator of similarity. We resolve the issue of over-plotting and increase the utility of the widely-used parallel coordinates visualization. © 2013 Springer-Verlag Berlin Heidelberg.


Gade W.,One University Place | Schmit J.,One University Place | Collins M.,One University Place | Gade J.,One University Place
Clinical laboratory science : journal of the American Society for Medical Technology | Year: 2010

Metabolic syndrome (MSX) identifies clinical symptoms and lab results, including abdominal obesity, insulin resistance, hyperglycemia, hyperlipidemia, and hypertension, that lead to an increased risk of cardiovascular disease (CVD). Obesity typically results in insulin and leptin resistance and a shift from expansion of subcutaneous fat to deposition of abdominal and ectopic fat. These conditions cause metabolic dysregulation, elevated fatty acids (FFA), and increased secretion of pro-inflammatory "adipokines". Left untreated, these conditions cause lipotoxicity, chronic inflammation, hypertension, atherosclerosis, and CVD.


PubMed | One University Place
Type: | Journal: BMC research notes | Year: 2014

Fusarochromanone (FC101) is a small molecule fungal metabolite with a host of interesting biological functions, including very potent anti-angiogenic and direct anti-cancer activity.Herein, we report that FC101 exhibits very potent in-vitro growth inhibitory effects (IC50 ranging from 10nM-2.5 M) against HaCat (pre-malignant skin), P9-WT (malignant skin), MCF-7 (low malignant breast), MDA-231 (malignant breast), SV-HUC (premalignant bladder), UM-UC14 (malignant bladder), and PC3 (malignant prostate) in a time-course and dose-dependent manner, with the UM-UC14 cells being the most sensitive. FC101 induces apoptosis and an increase in proportion of cells in the sub-G1 phase in both HaCat and P9-WT cell lines as evidenced by cell cycle profile analysis. In a mouse xenograft SCC tumor model, FC101 was well tolerated, non-toxic, and achieved a 30% reduction in tumor size at a dose of 8 mg/kg/day. FC101 is also a potent anti-angiogenenic agent. At nanomolar doses, FC101 inhibits the vascular endothelial growth factor-A (VEGF-A)-mediated proliferation of endothelial cells.Our data presented here indicates that FC101 is an excellent lead candidate for a small molecule anti-cancer agent that simultaneously affects angiogenesis signaling, cancer signal transduction, and apoptosis. Further understanding of the underlying FC101s molecular mechanism may lead to the design of novel targeted and selective therapeutics, both of which are pursued targets in cancer drug discovery.


PubMed | One University Place and LSU Shreveport
Type: Journal Article | Journal: In silico pharmacology | Year: 2016

For 30years nature has provided a plethora of natural products with potential meaningful anti-cancer activity. Fusarochromanone (FC101a) is a small molecule fungal metabolite exhibiting potent in-vitro growth inhibitory effects and is capable of inducing apoptosis, suppressing angiogenesis and tumorigenesis, and inhibiting endothelial cell growth in multiple cancer cell lines. Despite all we know regarding FC101a, the mechanism of action and molecular target(s) of this compound have remained an enigma. Furthermore, modest in-vivo activity has been documented and requires addressing.Early stage pharmacokinetics (PK) assessment is vital to successful drug development. Herein, we aimed to use in-silico assays to i) characterize an in-depth ADMET profile of FC101a and ii) to probe for possible therapeutic targets. Two-dimensional SDF files of FC101a and 13 analogs were introduced into ADMET Predictor Version 7.1 that parses the structures in order to calculate molecular descriptors, which are used to estimate ADMET properties. Calculated ADMET values were analyzed and subjected to multiple drug-like indices, delivering a PK profile of each analog. To probe for possible targets, a total of 49 proteins were introduced into SYBYL-X Version 2.0 platform and the deepest binding pocket of each protein was virtually docked with parent compound, FC101a; with the negative control, FC101b; and with the model compound, kynurenine.Each analog showed promising ADMET qualities, although FC101 Oxazole was identified as the most optimized analog. Despite FC101a having a desirable ADME and toxicity profile, areas of concern were identified and must be addressed in-vitro. These include potential mutagenic properties and estrogen receptor toxicity. We provide potential avenues medicinal chemists could use to achieve higher effective permeation, higher blood brain barrier (BBB) penetration, and higher aqueous solubility in FC101a. Molecular docking assays revealed procaspase-8 - cFLIP(L) complex as a potential biological target and led to proposed mechanisms of action by which FC101a facilitates procaspase-8 heterodimerization, thereby increasing proteolytic activity and up regulating extrinsic apoptosis.Our data revealed both potential mechanisms of action and a promising ADMET profile of FC101a. These attributes render FC101a a promising lead candidate for development into a low toxic anti-cancer agent effective against a broad range of cancers.

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