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Apoptosis

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Full-Text Articles in Life Sciences

The Evolution Of Tumor Suppressing Genes In Multicellular Organisms: Nature’S Prevention Of Oncogenesis, Melanie Perez May 2024

The Evolution Of Tumor Suppressing Genes In Multicellular Organisms: Nature’S Prevention Of Oncogenesis, Melanie Perez

FIU Undergraduate Research Journal

The p53 gene family, a well-known group of genes, is the primary propagator of tumor-suppressing mechanisms in multicellular organisms. Although they are currently critical drug targets in cancer, the p53 family also serves specific functions in the development of multicellular organisms. In this paper, the current function, origin, and evolutionary purpose of the p53 family are reviewed in the evolution of multicellular organisms. The TP53 gene induces cellular responses such as apoptosis as a way to combat detrimental environmental and cellular factors that can damage the integrity of a cell’s DNA. The other two members of the p53 family are …


Investigating The Therapeutic Potential Of Soursop In Treating Hematologic Malignancies, Sabrina Marie Paparo, Rebeca Mendoza, Robert Chitren, Omar Al-Odat, Emily Nelson, Subash Jonnalagadda, Roger Strair, Manoj Pandey May 2024

Investigating The Therapeutic Potential Of Soursop In Treating Hematologic Malignancies, Sabrina Marie Paparo, Rebeca Mendoza, Robert Chitren, Omar Al-Odat, Emily Nelson, Subash Jonnalagadda, Roger Strair, Manoj Pandey

Rowan-Virtua Research Day

Acute Myeloid Leukemia (AML) and Multiple Myeloma (MM) are hematologic malignancies that originate in the bone marrow and account for approximately 1.3% and 2% of cancer cases, respectively. AML is characterized by an accumulation of myeloblasts, or immature myeloid cells, that have the potential to spread to the peripheral blood. There is an uncontrolled proliferation of plasma cells in the bone marrow in MM. While the current treatment options for both AML and MM show promise in achieving initial remission, it is unfortunately common for patients to experience relapse and develop drug resistance. There is a theory that relapse and …


Bcl2 Mediated Targeted Drug Delivery For The Treatment Of Kidney Fibrosis And Stomach Cancer, Humayra Afrin May 2024

Bcl2 Mediated Targeted Drug Delivery For The Treatment Of Kidney Fibrosis And Stomach Cancer, Humayra Afrin

Open Access Theses & Dissertations

Apoptosis, the programmed death of cells, is primarily regulated by a delicate balance between pro-apoptotic and anti-apoptotic signals. The Bcl-2 (B-cell lymphoma 2) family of proteins acts as anti-apoptotic agents, promoting cell survival. Dysregulation of these proteins is a common occurrence in conditions such as cancer and fibrosis, where overexpression of anti-apoptotic members can foster tumor cell survival and fibroblast activation. In this study, our aim was to explore the therapeutic potential of Bcl-2 inhibitors, both as a small molecule (specifically Navitoclax (Navi)), inhibitor and as Bcl-2 siRNA, for targeted treatment. Intravenous administration of Navi often leads to thrombocytopenia, necessitating …


Honey Targets Ribosome Biogenesis Process In Human Pancreatic Cancer Cells To Inhibit Their Growth And Metastatic Phenotypes, Aun A. Bangash, Muhammad Bangash, Haider Ahsan, Shiza Khan, Mudassier Ahmad, Dae Joon Kim, Sahir Alvi, Bilal B. B. Hafeez Mar 2024

Honey Targets Ribosome Biogenesis Process In Human Pancreatic Cancer Cells To Inhibit Their Growth And Metastatic Phenotypes, Aun A. Bangash, Muhammad Bangash, Haider Ahsan, Shiza Khan, Mudassier Ahmad, Dae Joon Kim, Sahir Alvi, Bilal B. B. Hafeez

Research Symposium

Background: Pancreatic cancer (PanCa) is the fourth deadliest cancer worldwide and is expected to become the second deadliest cancer by 2030. In the USA, the National Cancer Institute put forth a grim prediction stating that there will be 64,050 new cases in 2023 alone and about 50,000 of these patients will die. Existing therapeutic regimens against PanCa are not that effective and show unacceptable toxicities. Therefore, developing highly effective new agents with less toxicity is urgently required, which could be used as a monotherapy or as an adjuvant to treat PanCa patients. Honey is known for its tremendous health benefits …


Solving The Hiv Enigma: Investigating Mutant Long-Term Non-Progressor Vpr Strands, Megan Knight, Bradford Berges Mar 2024

Solving The Hiv Enigma: Investigating Mutant Long-Term Non-Progressor Vpr Strands, Megan Knight, Bradford Berges

Library/Life Sciences Undergraduate Poster Competition 2024

Different variants of HIV:

➢ Rapid Progressor: aggressive symptoms, quick progression into AIDs

➢ Wild-Type: regular symptoms, regular progression into AIDs

➢ Long-Term Non-Progressor: little-


Expression Patterns Of M6a Rna Methylation Regulators Under Apoptotic Conditions In Various Human Cancer Cell Lines, Azime Akçaöz Alasar, Buket Sağlam, İpek Erdoğan Vatansever, Bünyamin Akgül Feb 2024

Expression Patterns Of M6a Rna Methylation Regulators Under Apoptotic Conditions In Various Human Cancer Cell Lines, Azime Akçaöz Alasar, Buket Sağlam, İpek Erdoğan Vatansever, Bünyamin Akgül

Turkish Journal of Biology

Background/aim: Cancer is a complex disease that involves both genetic and epigenetic factors. While emerging evidence clearly suggests that changes in epitranscriptomics play a crucial role in cancer pathogenesis, a comprehensive understanding of the writers, erasers, and readers of epitranscriptomic processes, particularly under apoptotic conditions remains lacking. The aim of this study was to uncover the changes in the expression of m6A RNA modifiers under apoptotic conditions across various cancer cell lines. Materials and methods: Initially, we quantified the abundance of m6A RNA modifiers in cervix (HeLa and ME180), breast (MCF7 and MDA-MB-231), lung (A549 and H1299), and colon (CaCo2 …


Evidence Of Direct Interaction Between Cisplatin And The Caspase-Cleaved Prostate Apoptosis Response-4 Tumor Suppressor, Krishna K. Raut, Samjhana Pandey, Gyanendra Kharel, Steven M. Pascal Jan 2024

Evidence Of Direct Interaction Between Cisplatin And The Caspase-Cleaved Prostate Apoptosis Response-4 Tumor Suppressor, Krishna K. Raut, Samjhana Pandey, Gyanendra Kharel, Steven M. Pascal

Chemistry & Biochemistry Faculty Publications

Prostate apoptosis response-4 (Par-4) tumor suppressor protein has gained attention as a potential therapeutic target owing to its unique ability to selectively induce apoptosis in cancer cells, sensitize them to chemotherapy and radiotherapy, and mitigate drug resistance. It has recently been reported that Par-4 interacts synergistically with cisplatin, a widely used anticancer drug. However, the mechanistic details underlying this relationship remain elusive. In this investigation, we employed an array of biophysical techniques, including circular dichroism spectroscopy, dynamic light scattering, and UV–vis absorption spectroscopy, to characterize the interaction between the active caspase-cleaved Par-4 (cl-Par-4) fragment and cisplatin. Additionally, elemental analysis was …


Synergistic Effects Of Nanosecond Pulsed Plasma And Electric Field On Inactivation Of Pancreatic Cancer Cells In Vitro, Edwin A. Oshin, Zobia Minhas, Ruben M. L. Colunga Biancatelli, John D. Catravas, Richard Heller, Siqi Guo, Chunqi Jiang Jan 2024

Synergistic Effects Of Nanosecond Pulsed Plasma And Electric Field On Inactivation Of Pancreatic Cancer Cells In Vitro, Edwin A. Oshin, Zobia Minhas, Ruben M. L. Colunga Biancatelli, John D. Catravas, Richard Heller, Siqi Guo, Chunqi Jiang

Bioelectrics Publications

Nanosecond pulsed atmospheric pressure plasma jets (ns-APPJs) produce reactive plasma species, including charged particles and reactive oxygen and nitrogen species (RONS), which can induce oxidative stress in biological cells. Nanosecond pulsed electric field (nsPEF) has also been found to cause permeabilization of cell membranes and induce apoptosis or cell death. Combining the treatment of ns-APPJ and nsPEF may enhance the effectiveness of cancer cell inactivation with only moderate doses of both treatments. Employing ns-APPJ powered by 9 kV, 200 ns pulses at 2 kHz and 60-nsPEF of 50 kV/cm at 1 Hz, the synergistic effects on pancreatic cancer cells (Pan02) …


Cryptocaryone Induces Apoptosis In Human Hepatocellular Carcinoma Cells By Inhibiting Aerobic Glycolysis Through Akt And C-Src Signaling Pathways, Chen-Lin Yu, Yu-Wei Lai, Jih-Jung Chen, Jie-Jen Lee, Tsung-Hsien Chou, Chen-Chen Huang, Shih-Chia Liu, Guang-Wei Chen, Chung‐Hsin Tsai, Shih-Wei Wang Dec 2023

Cryptocaryone Induces Apoptosis In Human Hepatocellular Carcinoma Cells By Inhibiting Aerobic Glycolysis Through Akt And C-Src Signaling Pathways, Chen-Lin Yu, Yu-Wei Lai, Jih-Jung Chen, Jie-Jen Lee, Tsung-Hsien Chou, Chen-Chen Huang, Shih-Chia Liu, Guang-Wei Chen, Chung‐Hsin Tsai, Shih-Wei Wang

Journal of Food and Drug Analysis

Hepatocellular carcinoma (HCC) is the most common form of liver cancer, with the second highest mortality rate in all cancer. Energy reprogramming is one of the hallmarks of cancer, and emerging evidence showed that targeting glycolysis is a promising strategy for HCC treatment. Cryptocaryone has been shown to display promising anti-cancer activity against numerous types of cancer. Previous study also indicated that cryptocaryone induces cytotoxicity by inhibiting glucose transport in cancer cells, but the detailed mechanism still needs to be elucidated. Therefore, this study aimed to investigate the relationship between the anti-cancer effect and glycolytic metabolism of cryptocaryone in human …


Steamed Daylily Flower (Hemerocallis Fulva L.) Protected Cardiac And Hepatic Cells Against Ethanol Induced Apoptotic And Oxidative Damage, Sheng-Lei Yan, Wen-Tzu Wu, Mei-Chin Mong, Mei-Chin Yin Dec 2023

Steamed Daylily Flower (Hemerocallis Fulva L.) Protected Cardiac And Hepatic Cells Against Ethanol Induced Apoptotic And Oxidative Damage, Sheng-Lei Yan, Wen-Tzu Wu, Mei-Chin Mong, Mei-Chin Yin

Journal of Food and Drug Analysis

Our previous study examined the phytochemical composition and bio-activities of raw daylily flower (Hemerocallis fulva L.). However, this plant food is usually served via heat process such as cooking in a soup. This study aimed to investigate the phytochemical profile and biofunctions of steamed daylily flower (SDF). The content of total phenolic acids, total flavonoids, total carotenoids, total anthocyanins and total triterpenoids in SDF aqueous extract was assessed. Normal cardiac and hepatic cells, H9c2 and L-02 cells, were used to evaluate the protective effects of SDF against ethanol. SDF concentrations of 0.25%, 0.5%, and 1% were applied to treat …


Changes In Rna Expression Of Hut78 Cells Resulting From The Hiv-1 Viral Protein R R77q Mutation, Joshua S. Ramsey Oct 2023

Changes In Rna Expression Of Hut78 Cells Resulting From The Hiv-1 Viral Protein R R77q Mutation, Joshua S. Ramsey

Theses and Dissertations

Human immunodeficiency virus type 1 (HIV-1) is the causative virus for acquired immunodeficiency syndrome (AIDS). AIDS is characterized by chronic inflammation and reduction of CD4+ T-cells in the blood. This leads to the patient becoming immunocompromised and much more susceptible to disease in general. Different phenotypes in the progression of AIDS have been observed in patients in either progressing to AIDS faster as a Rapid Progressor (RP), or slower as a Long-Term Non-Progressor (LTNP). Researching elements that result in the LTNP phenotype is of interest as it has the potential to offer alternative treatments and therapies to those suffering from …


Piperine Encourages Apoptosis In Human Cervical Adenocarcinoma Cells Through Ros Generation, Dna Fragmentation, Caspase-3 Activation And Cell Cycle Arrest, Asif Jafri, Juhi Rais, Sudhir Kumar, Md Arshad Sep 2023

Piperine Encourages Apoptosis In Human Cervical Adenocarcinoma Cells Through Ros Generation, Dna Fragmentation, Caspase-3 Activation And Cell Cycle Arrest, Asif Jafri, Juhi Rais, Sudhir Kumar, Md Arshad

Research Symposium

Background: Cancer is one of the most common destructive diseases and the second leading cause of death in humans. Among cancer, cervical cancer is the second most common malignancy among women globally. Thus, there is a continuous need to search for chemotherapeutic chemicals or naturally occurring drugs to resolve this global health problem. Piperine (1-piperoylpeperdine) is present in the fruits of black pepper (Piper nigrum Linn.) and long pepper (Piper longum Linn.). It possesses several pharmacological properties and in the present study we have evaluated its anti-cancer potential on human cervical adenocarcinoma (HeLa) cells.

Methods: The anti-proliferative effect …


Cyclophosphamide And Epirubicin Induce Apoptotic Cell Death In Microglia Cells, Rafael De La Hoz-Camacho Sep 2023

Cyclophosphamide And Epirubicin Induce Apoptotic Cell Death In Microglia Cells, Rafael De La Hoz-Camacho

Research Symposium

Background. Chemotherapy Related Cognitive Impairment’s (CRCI), diminish patient’s quality life, being breast cancer (BC) patients the most affected. Microglia is described to play a major role in CRCI; hence, the aim of this research was to describe the cytotoxicity of cyclophosphamide (CTX) and Epirubicin (EPI), on microglia (SIM-A9), compared to BC cells (4T1).

Methods. We assessed cell viability (Resazurin) and cell death (AnnV), as well as nuclear damage with γ-H2AX, p53, p16 and cell cycle analysis (PI staining) by flow cytometry (FC). Furthermore, we evaluated ΔΨm (DIOC6), ROS (DCFDA) and NO (DAF-FM) production. Finally, caspase activation (TF2-VAD-FMK) and autophagy (CYTO-ID). …


Molecular Event In Hrp Apoptosis, Laura Valdez Sep 2023

Molecular Event In Hrp Apoptosis, Laura Valdez

Research Symposium

Background: Human retinal pericytes (HRP) are contractile cells adjacent to and provide support for endothelial cells (EC) of capillaries, which are essential in the regulation of retinal vasculature. Early stages of DR are characterized by the loss of HRP, which leads to the development of advanced-stage pathology including angiogenesis. Although much is known about the etiology of DR, the apoptotic pathway that incites HRP loss remains unclear. Our preliminary studies reveal that monocyte-derived macrophages secrete TGF-β1, which induces the expression and secretion of a TGF-β1-Induced, pro-apoptotic BIGH3 protein (TGF-β–Induced Gene Human Clone 3) leading to apoptosis of HRP Eye, 30(12), …


A Naturally Derived Watercress Flower-Based Phenethyl Isothiocyanate-Enriched Extract Induces The Activation Of Intrinsic Apoptosis Via Subcellular Ultrastructural And Ca2+ Efflux Alterations In An In Vitro Model Of Human Malignant Melanoma, Sotiris Kyriakou, Louiza Potamiti, Nikoletta Demosthenous, Tom Amery, Kyle Stewart, Paul G. Winyard, Rodrigo Franco, Aglaia Pappa, Mihalis I. Panayiotidis Sep 2023

A Naturally Derived Watercress Flower-Based Phenethyl Isothiocyanate-Enriched Extract Induces The Activation Of Intrinsic Apoptosis Via Subcellular Ultrastructural And Ca2+ Efflux Alterations In An In Vitro Model Of Human Malignant Melanoma, Sotiris Kyriakou, Louiza Potamiti, Nikoletta Demosthenous, Tom Amery, Kyle Stewart, Paul G. Winyard, Rodrigo Franco, Aglaia Pappa, Mihalis I. Panayiotidis

School of Veterinary and Biomedical Sciences: Faculty Publications

The aim of the current study was to (i) extract isolated fractions of watercress flowers enriched in polyphenols, phenethyl isothiocyanate and glucosinolates and (ii) characterize the anticancer mode of action of non-lethal, sub-lethal and lethal concentrations of the most potent extract fraction in primary (A375) and metastatic (COLO-679) melanoma cells as well as non-tumorigenic immortalized keratinocyte (HaCaT) cells. Cytotoxicity was assessed via the Alamar Blue assay, whereas ultrastructural alterations in mitochondria and the endoplasmic reticulum were determined via transmission electron microscopy. Mitochondrial membrane depolarization was determined using Mito-MP dye, whereas apoptosis was evaluated through the activation of caspases-3, -8 and …


Expression Of Hif-1Α, Caspase-3, P53, Hsp70, Hsp90, And Nrf2 In The Canine Spleen With Siderofibrotic Nodules: An Immunohistochemical And Immunofluorescence Perspective On Apoptosis, Ferroptosis, And Oxidative Stress, Ali Babanezhad-Gajouti, Amir Amniattalab Aug 2023

Expression Of Hif-1Α, Caspase-3, P53, Hsp70, Hsp90, And Nrf2 In The Canine Spleen With Siderofibrotic Nodules: An Immunohistochemical And Immunofluorescence Perspective On Apoptosis, Ferroptosis, And Oxidative Stress, Ali Babanezhad-Gajouti, Amir Amniattalab

Turkish Journal of Veterinary & Animal Sciences

Splenic siderofibrotic nodules (SFNs) are benign tiny yellow-brownish foci found in dogs. Their pathogenesis is unclear whereas trauma and hemorrhage are assumed to be the possible causative factors. The spleen of 73 Iranian dogs of the mixed breed was examined for possible splenomegaly with SFNs. Ultrasonography, blood biochemistry, pathology, and immunohistochemistry revealed splenomegaly (n = 7), splenomegaly with SFNs (n = 6) and normal spleens (n = 60). There was no significant difference between the prevalence of splenomegaly with SFN among the examined dogs and their age or sex (p > 0.05). Ultrasonography represented a significant increase (p ≤ 0.01) in …


Soloxolone Methyl Induces Apoptosis And Oxidative/Er Stress In Breast Cancer Cells And Target Cancer Stem Cell Population, Eli̇f Ertürk, Oğuzhan Akgün, Yaren Yildiz, Pinar Kalkan, Oksana V. Salomatina, Nariman F. Salakhutdinov, Engi̇n Ulukaya, Ferda Ari Aug 2023

Soloxolone Methyl Induces Apoptosis And Oxidative/Er Stress In Breast Cancer Cells And Target Cancer Stem Cell Population, Eli̇f Ertürk, Oğuzhan Akgün, Yaren Yildiz, Pinar Kalkan, Oksana V. Salomatina, Nariman F. Salakhutdinov, Engi̇n Ulukaya, Ferda Ari

Turkish Journal of Biology

One of the most prevalent malignancies in women and one of the leading causes of cancer-related death is breast cancer. There is a need for new treatment approaches and drugs for breast cancer. Many studies show the high potential of triterpene compounds and their semisynthetic derivatives as anticancer agents due to their ability to induce apoptosis and suppress tumorigenesis. The effects of soloxolone methyl (SM), a semisynthetic derivative of 18-H-glycyrrhetinic acid, on the cytotoxicity and apoptosis of human breast cancer cell line (T-47D) and cancer stem cell (CSCs) population (mammospheres; CD44+/CD24-antigen) derived from breast cancer cells, were examined in this …


Antileukemic Potential Of Nile Blue-Mediated Photodynamic Therapy On Hl60 Human Myeloid Leukemia Cells, Serçi̇n Özlem Çalişkan, Aynur Karadağ, Bariş Uzunok, Numan Taşpinar, Berna Akin, Meti̇n Çalişkan, Rahşan Ilikçi Sağkan Aug 2023

Antileukemic Potential Of Nile Blue-Mediated Photodynamic Therapy On Hl60 Human Myeloid Leukemia Cells, Serçi̇n Özlem Çalişkan, Aynur Karadağ, Bariş Uzunok, Numan Taşpinar, Berna Akin, Meti̇n Çalişkan, Rahşan Ilikçi Sağkan

Turkish Journal of Biology

Background/aim: Photodynamic therapy (PDT) has received great attention over the past decade in the treatment of diseases such as leukemia which is a cancer of the blood and bone marrow cells that causes a significant number of deaths worldwide. In this study, it was aimed to investigate the effects of Nile blue-mediated PDT (NB-mediated PDT) on HL60 cells. Materials and methods: The effect of NB-mediated PDT on cell proliferation was evaluated with cell volume analysis using flow cytometry at 24 h. Cell apoptosis, ROS production, mitochondrial membrane potential, and cell cycle analysis were evaluated using annexin V-FITC, H2 DCFDA, JC-1, …


Effects Of High Glucose On Autophagy And Apoptosis In Preimplantation Mouse Embryo Culture, Virginia Wolfe Jun 2023

Effects Of High Glucose On Autophagy And Apoptosis In Preimplantation Mouse Embryo Culture, Virginia Wolfe

Electronic Thesis and Dissertation Repository

Maternal diabetes increases congenital malformations due to teratogenic effects of glucose on the developing embryo. High glucose culture alters preimplantation embryo development and is associated with increased oxidative stress. Apoptosis and autophagy are programmed cell death and survival mechanisms induced by oxidative stress, but their role in preimplantation diabetic embryopathy is poorly elucidated. It was hypothesized that high glucose culture would alter autophagic and apoptotic responses, and that they are dependent on the timing of high glucose culture initiation. Embryos were cultured with 0.2 mM (control) or 25 mM (high glucose) of D-glucose starting from the early (36 hpi) or …


The Inhibitory Effect Of Quercetin-3-Glucuronide On Pulmonary Injury In Vitro And In Vivo, Pei-Rong Yua, Jen-Ying Hsu, Chiao-Yun Tseng, Jing-Hsien Chen, Hui-Hsuan Lin Jun 2023

The Inhibitory Effect Of Quercetin-3-Glucuronide On Pulmonary Injury In Vitro And In Vivo, Pei-Rong Yua, Jen-Ying Hsu, Chiao-Yun Tseng, Jing-Hsien Chen, Hui-Hsuan Lin

Journal of Food and Drug Analysis

Pulmonary injury is defined as a progressive inflammation. Extensive pro-inflammatory cytokines are secreted from alveolus, associated with the production of reactive oxygen species (ROS) and apoptosis. The model of endotoxin lipopolysaccharide (LPS)-stimulated lung cells has been applied to mimic the pulmonary injury. Some antioxidants and anti-inflammatory compounds can be used as chemopreventive agents of pulmonary injury. Quercetin-3-glucuronide (Q3G) has been showed to exert antioxidant, anti-inflammatory, anti-cancer, anti-aging and anti-hypertension effects. The aim of the study is to examine the inhibitory potential of Q3G on pulmonary injury and inflammation in vitro and in vivo. Firstly, human lung fibroblasts MRC-5 cells pre-treated …


Mycobacterium Avium Subsp. Paratuberculosis Candidate Vaccine Strains Are Pro-Apoptotic In Raw264.7murinemacrophages, Raul G. Barletta, John P. Bannantine, Judith R. Stabel, Ezhumalai Muthukrishnan, Dirk Anderson, Enakshy Dutta, Vamsi Manthena, Mostafa Hanafy, Denise K. Zinniel Jun 2023

Mycobacterium Avium Subsp. Paratuberculosis Candidate Vaccine Strains Are Pro-Apoptotic In Raw264.7murinemacrophages, Raul G. Barletta, John P. Bannantine, Judith R. Stabel, Ezhumalai Muthukrishnan, Dirk Anderson, Enakshy Dutta, Vamsi Manthena, Mostafa Hanafy, Denise K. Zinniel

School of Veterinary and Biomedical Sciences: Faculty Publications

Mycobacterium avium subsp. paratuberculosis (MAP) is the etiological agent of Johne’s disease, a severe gastroenteritis of ruminants. This study developed a model cell culture system to rapidly screen MAP mutants with vaccine potential for apoptosis. Two wild-type strains, a transposon mutant, and two deletion mutant MAP strains (MOI of 10 with 1.2 × 106 CFU) were tested in murine RAW 264.7 macrophages to determine if they induce apoptosis and/or necrosis. Both deletion mutants were previously shown to be attenuated and immunogenic in primary bovine macrophages. All strains had similar growth rates, but cell morphology indicated that both deletion mutants …


Investigation Into The Enhanced Activation Of The Are And The Correlations Between Nrf2 And Other Cytoprotective Pathways Such As Ahr, Hsp, And Apoptosis, Jonathon Joseph Odom Jun 2023

Investigation Into The Enhanced Activation Of The Are And The Correlations Between Nrf2 And Other Cytoprotective Pathways Such As Ahr, Hsp, And Apoptosis, Jonathon Joseph Odom

Doctoral Dissertations and Projects

Oxidative damage is a cellular threat that is responsible for many pathologic conditions such as Alzheimer’s disease, Parkinson’s disease, chronic obstructive pulmonary disease (COPD), cancer, and many more. The primary cytoprotective pathway within the cell that is responsible for mitigating the harmful effects of oxidative stress is the antioxidant system. The master regulator of the antioxidant system is the transcription factor, nuclear factor erythroid 2-related factor 2 (NRF2) which operates by binding to the antioxidant response element (ARE) and inducing the production of many antioxidant genes. It is known that the early response of NRF2 is regulated by electrophilic interaction …


Design, Synthesis, And Antiproliferative Activity Of Benzopyran-4-One-Isoxazole Hybrid Compounds, Shilpi Gupta, Shang Eun Park, Saghar Mozaffari, Bishoy El-Aarag, Keykavous Parang, Rakesh Kumar Tiwari May 2023

Design, Synthesis, And Antiproliferative Activity Of Benzopyran-4-One-Isoxazole Hybrid Compounds, Shilpi Gupta, Shang Eun Park, Saghar Mozaffari, Bishoy El-Aarag, Keykavous Parang, Rakesh Kumar Tiwari

Pharmacy Faculty Articles and Research

The biological significance of benzopyran-4-ones as cytotoxic agents against multi-drug resistant cancer cell lines and isoxazoles as anti-inflammatory agents in cellular assays prompted us to design and synthesize their hybrid compounds and explore their antiproliferative activity against a panel of six cancer cell lines and two normal cell lines. Compounds 5ad displayed significant antiproliferative activities against all the cancer cell lines tested, and IC50 values were in the range of 5.2–22.2 μM against MDA-MB-231 cancer cells, while they were minimally cytotoxic to the HEK-293 and LLC-PK1 normal cell lines. The IC50 values of 5ad …


Is Vdac1 A Novel Bcl2 Family Member That Binds Bax?, Claire Pearson May 2023

Is Vdac1 A Novel Bcl2 Family Member That Binds Bax?, Claire Pearson

Honors Theses

Apoptosis is a type of regulated cell death important for normal embryonic development and maintenance of adult tissues by removing excess or dysfunctional cells to ensure proper functioning of organs. The Bcl-2 family of proteins determines whether apoptosis remains suppressed or becomes activated through the balance of interactions among pro-survival and pro-death members. A defining feature of the Bcl-2 family is a BH3 domain that drives interactions between the family members. Isoform 1 of the voltage dependent anion channel (VDAC1) has an important role in metabolism, but was recently found to have high homology with known BH3 domains. This study …


Does Vdac2 Have A Bh3 Domain?, Lillian Ferkany May 2023

Does Vdac2 Have A Bh3 Domain?, Lillian Ferkany

Honors Theses

Mitochondrial outer membrane permeabilization (MOMP) by Bax oligomerization triggers apoptosis. BCl-2 family proteins, classified as BH3 only proteins, pro-survival proteins, or pro-apoptotic proteins, control apoptosis partly through their agonist or antagonistic effects on Bax, which are mediated by their conserved BH3 domains. All BH3 domains form an alpha helix containing 5-7 conserved hydrophobic residues, designated H0-H5, and one conserved aspartic acid that drive interaction with Bax and other ‘multi-domain’ BCl-2 members. BH3 agonists induce Bax oligomerization, while BH3 antagonists sequester Bax to prevent MOMP. We discovered that voltage dependent anion channels (VDACs) in the MOM contain a putative BH3-like domain …


Apoptosis Induction In Jurkat T-Lymphocytes By Proton Pump Inhibitors (Ppis), Shreya Murali, Randall Reif Apr 2023

Apoptosis Induction In Jurkat T-Lymphocytes By Proton Pump Inhibitors (Ppis), Shreya Murali, Randall Reif

Student Research Submissions

Apoptosis, commonly known as programmed cell death, constantly occurs in humans. As a cancer cell increases in acidity, apoptosis is induced. In healthy cells, proton pump proteins allow for H+ ions to permeate cellular membranes, regulating pH. However, proton pump inhibitors (PPIs), such as omeprazole, prevent proton movement. In previous studies, omeprazole induced cell death in Jurkat T lymphocytes; however, there was no confirmation of whether the cells died through apoptosis, or through necrosis, where the cell bursts. By using Annexin-V staining, the effects of omeprazole, dexlansoprazole, and esomeprazole on apoptosis induction can be measured. Cell death was observed …


Histone Deacetylase 8 Is A Novel Therapeutic Target For Mantle Cell Lymphoma And Preserves Natural Killer Cell Cytotoxic Function, January M. Watters Mar 2023

Histone Deacetylase 8 Is A Novel Therapeutic Target For Mantle Cell Lymphoma And Preserves Natural Killer Cell Cytotoxic Function, January M. Watters

USF Tampa Graduate Theses and Dissertations

This study demonstrates for the first time that HDAC8 function is critical for MCL survival, and abrogating its activity in human primary NK cells does not interfere with NK IgG antibody directed ADCC therapies ex vivo. Human NK cells, isolated from healthy donors, are highly resistant to HDAC8 inhibitor treatment with PCI-34051. Even at the highest concentration, 20uM, no toxicity was observed. Conversely, MCL cell lines representative of the aggressive MCL subtype, classical MCL, were especially sensitive to PCI-34051, an HDAC8 selective inhibitor, treatment. Blocking HDAC8 activity and/or abrogating expression through shRNA silencing induced significant DNA damage, hyperacetylation of SMC3, …


Modulation Of Rna Splicing Enhances Response To Bcl2 Inhibition In Leukemia., Eric Wang, Jose Mario Bello Pineda, Won Jun Kim, Sisi Chen, Jessie Bourcier, Maximilian Stahl, Simon J Hogg, Jan Phillipp Bewersdorf, Cuijuan Han, Michael E Singer, Daniel Cui, Caroline E Erickson, Steven M Tittley, Alexander V Penson, Katherine Knorr, Robert F Stanley, Jahan Rahman, Gnana Krishnamoorthy, James A Fagin, Emily Creger, Elizabeth Mcmillan, Chi-Ching Mak, Matthew Jarvis, Carine Bossard, Darrin M Beaupre, Robert K Bradley, Omar Abdel-Wahab Jan 2023

Modulation Of Rna Splicing Enhances Response To Bcl2 Inhibition In Leukemia., Eric Wang, Jose Mario Bello Pineda, Won Jun Kim, Sisi Chen, Jessie Bourcier, Maximilian Stahl, Simon J Hogg, Jan Phillipp Bewersdorf, Cuijuan Han, Michael E Singer, Daniel Cui, Caroline E Erickson, Steven M Tittley, Alexander V Penson, Katherine Knorr, Robert F Stanley, Jahan Rahman, Gnana Krishnamoorthy, James A Fagin, Emily Creger, Elizabeth Mcmillan, Chi-Ching Mak, Matthew Jarvis, Carine Bossard, Darrin M Beaupre, Robert K Bradley, Omar Abdel-Wahab

Faculty Research 2022

Therapy resistance is a major challenge in the treatment of cancer. Here, we performed CRISPR-Cas9 screens across a broad range of therapies used in acute myeloid leukemia to identify genomic determinants of drug response. Our screens uncover a selective dependency on RNA splicing factors whose loss preferentially enhances response to the BCL2 inhibitor venetoclax. Loss of the splicing factor RBM10 augments response to venetoclax in leukemia yet is completely dispensable for normal hematopoiesis. Combined RBM10 and BCL2 inhibition leads to mis-splicing and inactivation of the inhibitor of apoptosis XIAP and downregulation of BCL2A1, an anti-apoptotic protein implicated in venetoclax resistance. …


Mitoq Alleviates Hippocampal Damage After Cerebral Ischemia: The Potential Role Of Sirt6 In Regulating Mitochondrial Dysfunction And Neuroinflammation, Ayman A. Ibrahim, Sherif S. Abdel Mageed Dr, Marwa M. Safar Prof.Dr, Mohammed F. El-Yamany Prof.Dr., Mamdouh A. Oraby Dr. Jan 2023

Mitoq Alleviates Hippocampal Damage After Cerebral Ischemia: The Potential Role Of Sirt6 In Regulating Mitochondrial Dysfunction And Neuroinflammation, Ayman A. Ibrahim, Sherif S. Abdel Mageed Dr, Marwa M. Safar Prof.Dr, Mohammed F. El-Yamany Prof.Dr., Mamdouh A. Oraby Dr.

Pharmacy

Aims: Mitochondrial perturbations are the major culprit of the inflammatory response during the initial phase of cerebral ischemia. The present study explored the neuroprotective effect of the mitochondrial-targeted antioxidant, Mitoquinol (MitoQ), against hippocampal neuronal loss in an experimental model of brain ischemia/ reperfusion (I/R) injury. Main methods: Rats were subjected to common carotid artery occlusion for 45 min, followed by reperfusion for 24 h. MitoQ (2 mg/kg; i.p daily) was administered for 7 successive days prior to the induction of brain ischemia. Key findings: I/R rats exhibited hippocampal damage evidenced by aggravated mitochondrial oxidative stress, thereby enhancing mtROS and oxidized …


Chemical Characterization And Biological Evaluation Of Epilobium Parviflorum Extracts In An In Vitro Model Of Human Malignant Melanoma, Sotiris Kyriakou, Venetia Tragkola, Ioannis Paraskevaidis, Mihalis Plioukas, Dimitrios T. Trafalis, Rodrigo Franco, Aglaia Pappa, Mihalis I. Panayiotidi Jan 2023

Chemical Characterization And Biological Evaluation Of Epilobium Parviflorum Extracts In An In Vitro Model Of Human Malignant Melanoma, Sotiris Kyriakou, Venetia Tragkola, Ioannis Paraskevaidis, Mihalis Plioukas, Dimitrios T. Trafalis, Rodrigo Franco, Aglaia Pappa, Mihalis I. Panayiotidi

School of Veterinary and Biomedical Sciences: Faculty Publications

Malignant melanoma is an aggressive type of skin cancer characterised by high metastatic capacity and mortality rate. On the other hand, Epilobium parviflorum is known for its medicinal properties, including its anticancer potency. In this context, we aimed to (i) isolate various extracts of E. parviflorum, (ii) characterize their phytochemical content, and (iii) determine their cytotoxic potential in an in vitro model of human malignant melanoma. To these ends, we utilized various spectrophotometric and chromatographic (UPLC-MS/MS) approaches to document the higher content of the methanolic extract in polyphenols, soluble sugars, proteins, condensed tannins, and chlorophylls -a and -b as …