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Full-Text Articles in Biology
The Foxo1 Inhibitor As1842856 Triggers Apoptosis In Glioblastoma Multiforme And Basal-Like Breast Cancer Cells, David Flores, Alma Lopez, Shreya Udawant, Bonnie Gunn, Megan Keniry
The Foxo1 Inhibitor As1842856 Triggers Apoptosis In Glioblastoma Multiforme And Basal-Like Breast Cancer Cells, David Flores, Alma Lopez, Shreya Udawant, Bonnie Gunn, Megan Keniry
Biology Faculty Publications and Presentations
Basal-like breast cancer (BBC) and glioblastoma multiforme (GBM) are poor-prognosis cancers that lack effective targeted therapies and harbor embryonic stem gene expression signatures. Recently, our group and others found that forkhead box transcription factor FOXO1 promotes stem gene expression in BBC and GBM cell lines. Given the critical role of cancer stem cells in promoting cancer progression, we examined the impact of FOXO1 inhibition with AS1842856 (a cell-permeable small molecule that directly binds to unphosphorylated FOXO1 protein to block transcriptional regulation) on BBC and GBM cell viability. We treated a set of BBC and GBM cancer cell lines with increasing …
Mitochondrial Oma1 And Opa1 As Gatekeepers Of Organellar Structure/Function And Cellular Stress Response, Robert Gilkerson, Patrick De La Torre, Shaynah St. Vallier
Mitochondrial Oma1 And Opa1 As Gatekeepers Of Organellar Structure/Function And Cellular Stress Response, Robert Gilkerson, Patrick De La Torre, Shaynah St. Vallier
Biology Faculty Publications and Presentations
Mammalian mitochondria are emerging as a critical stress-responsive contributor to cellular life/death and developmental outcomes. Maintained as an organellar network distributed throughout the cell, mitochondria respond to cellular stimuli and stresses through highly sensitive structural dynamics, particularly in energetically demanding cell settings such as cardiac and muscle tissues. Fusion allows individual mitochondria to form an interconnected reticular network, while fission divides the network into a collection of vesicular organelles. Crucially, optic atrophy-1 (OPA1) directly links mitochondrial structure and bioenergetic function: when the transmembrane potential across the inner membrane (ΔΨm) is intact, long L-OPA1 isoforms carry out fusion of the mitochondrial …
Nvp-Bez235 Or Jaki Treatment Leads To Decreased Survival Of Examined Gbm And Bbc Cells, Neftali Vazquez, Alma Lopez, Victoria Cuello, Michael W. Persans, Erin Schuenzel, Wendy Innis-Whitehouse, Megan Keniry
Nvp-Bez235 Or Jaki Treatment Leads To Decreased Survival Of Examined Gbm And Bbc Cells, Neftali Vazquez, Alma Lopez, Victoria Cuello, Michael W. Persans, Erin Schuenzel, Wendy Innis-Whitehouse, Megan Keniry
Biology Faculty Publications and Presentations
Cancer cells almost universally harbor constitutively active Phosphatidylinositol-3 Kinase (PI3K) Pathway ac-tivity via mutation of key signaling components and/or epigenetic mechanisms. Scores of PI3K Pathway in-hibitors are currently under investigation as putative chemotherapeutics. However, feedback and stem cell mechanisms induced by PI3K Pathway inhibition can lead to reduced treatment efficacy. To address therapeutic barriers, we examined whether JAKi would reduce stem gene expression in a setting of PI3K Pathway inhibition in order to improve treatment efficacy. We targeted the PI3K Pathway with NVP-BEZ235 (dual PI3K and mTOR inhibitor) in combination with the Janus Kinase inhibitor JAKi in glioblastoma (GBM) and …
A Comparison Of Resveratrol And Other Polyphenolic Compounds On Notch Activation And Endothelial Cell Activity, Bryce Lafoya, Jordan A. Munroe, Allan R. Albig
A Comparison Of Resveratrol And Other Polyphenolic Compounds On Notch Activation And Endothelial Cell Activity, Bryce Lafoya, Jordan A. Munroe, Allan R. Albig
Biology Faculty Publications and Presentations
Resveratrol is a polyphenolic compound produced by plants which makes its way into the human diet through plant-based foods. It has been shown to provide many health benefits, helping to ward of age-related diseases and promoting cardiovascular health. Additionally, resveratrol is a potent activator of the Notch signaling pathway. While resveratrol receives the most attention as a polyphenolic nutraceutical, other compounds with similar structures may be more potent regulators of specific cellular processes. Here, we compare resveratrol, apigenin, chrysin, genistein, luteolin, myricetin, piceatannol, pterostilbene, and quercetin for their ability to regulate Notch signaling. In addition, we compare the ability of …
Constitutive Map-Kinase Activation Suppresses Germline Apoptosis In Nth-1 Dna Glycosylase Deficient C. Elegans, Henok Kassahun, Tamina Sengupta, Alfonso Schiavi, Suzanne Estes, Silvia Maglioni, Hanne K. Skjeldam, Katarzyna Arczewska, Nicole L. Brockway, Lars Eide, Natascia Ventura, Hilde Nilsen
Constitutive Map-Kinase Activation Suppresses Germline Apoptosis In Nth-1 Dna Glycosylase Deficient C. Elegans, Henok Kassahun, Tamina Sengupta, Alfonso Schiavi, Suzanne Estes, Silvia Maglioni, Hanne K. Skjeldam, Katarzyna Arczewska, Nicole L. Brockway, Lars Eide, Natascia Ventura, Hilde Nilsen
Biology Faculty Publications and Presentations
Oxidation of DNA bases, an inevitable consequence of oxidative stress, requires the base excision repair (BER) pathway for repair. Caenorhabditis elegans is a well-established model to study phenotypic consequences and cellular responses to oxidative stress. To better understand how BER affects phenotypes associated with oxidative stress, we characterised the C. elegans nth-1 mutant, which lack the only DNA glycosylase dedicated to repair of oxidative DNA base damage, the NTH-1 DNA glycosylase. We show that nth-1 mutants have mitochondrial dysfunction characterised by lower mitochondrial DNA copy number, reduced mitochondrial membrane potential, and increased steady-state levels of reactive oxygen species. Consistently, nth-1 …
The Role Of Caspases In Alzheimer's Disease; Potential Novel Therapeutic Opportunities, Troy T. Rohn
The Role Of Caspases In Alzheimer's Disease; Potential Novel Therapeutic Opportunities, Troy T. Rohn
Biology Faculty Publications and Presentations
Although apoptosis plays a critical role in molding the CNS into its final appearance and function, inappropriate activation of this pathway in the aging brain may contribute to neurodegeneration. In Alzheimer’s disease (AD), an overwhelming body of evidence supports the activation of apoptosis in general, and caspases specifically as an early event that may not only contribute to neurodegeneration but also promote the underlying pathology associated with this disease. Therefore, caspase inhibitors may provide an effective strategy for treating AD. However, despite the compelling evidence indicating a role for caspases in disease progression, chronic treatment with caspase inhibitors in animal …
Caspase Cleavage Of The Amyloid Precursor Protein Is Prevented After Overexpression Of Bcl-2 In A Triple Transgenic Mouse Model Of Alzheimer’S Disease, Debra K. Kumasaka, Veronica Galvan, Elizabeth Head, Troy T. Rohn
Caspase Cleavage Of The Amyloid Precursor Protein Is Prevented After Overexpression Of Bcl-2 In A Triple Transgenic Mouse Model Of Alzheimer’S Disease, Debra K. Kumasaka, Veronica Galvan, Elizabeth Head, Troy T. Rohn
Biology Faculty Publications and Presentations
A recent study demonstrated the lack of beta-amyloid (Aβ) plaque formation and accumulation of the amyloid precursor protein (APP) in a triple transgenic mouse model of Alzheimer’s disease (3xTg-AD) following overexpression of the anti-apoptotic protein, Bcl-2 (Rohn et al., J. Neurosci. 28: 3051-9, 2008). The supposition from that study was the accumulation of APP resulted from a decrease in caspase-mediated processing of APP. To determine a direct role for the caspase-cleavage of APP in 3xTg-AD mice, we designed a site-directed caspasecleavage antibody to APP and demonstrated it is a specific marker for caspase-cleaved APP. Application of this antibody revealed neuronal …