Pharmacology, Toxicology and Environmental Health Commons^™

Garambullo (Myrtillocactus Geometrizans) Reduces Cell Viability Via Apoptosis And Inhibits Colony Formation In Ht-29 And Sw480 Colon Cancer Cell Lines., López-Alvarez Guadalupe Soledad, Gutierrez-Silerio Gloria Yareli, García-Solís Pablo, Morales-Bárcenas Rocio, Sánchez-Pérez Yesennia, Hernández-Puga Ana Gabriela, Vergara-Castañeda Haydé Azeneth

Journal of Food and Drug Analysis

Garambullo (Myrtillocactus geometrizans) is a Mexican fruit rich in bioactive phytochemicals. Its fermented extract (FEG), obtained after in vitro gastrointestinal digestion and fermentation, was evaluated in HT-29 and SW480 colorectal cancer cells. FEG reduced cell viability (IC50: 2985 and 3200 μg/mL, respectively) and induced apoptosis and necrosis. In 3D assays, FEG inhibited colony formation, with complete suppression in HT-29 cells. Molecular docking further suggested that butyric acid identified in FEG interacts with Caspase-3 and RIPK1. These findings support the antiproliferative and pro-death effects of FEG in colorectal cancer models.

Evaluation Of The Mechanism Of Cell Death After Exposure To Amorphous Silicon Dioxide Nanoparticles In Rat Pleural Mesothelial Cells And Golden Syrian Hamsters, Rachel P. Renda

Theses and Dissertations

Amorphous Silicon Dioxide Nanoparticles (SiO2 NPs) are widely used in the industrial processes, chemical, and cosmetics industries. Amorphous SiO2 NPs are abundant in the earth’s crust and can be released into the air through industrial and manufacturing activities. Such particles are overlooked and not as commonly studied when compared to their crystalline counterpart. Amorphous SiO2 NPs are pulmonary toxicants; however, the mechanism of toxicity is uncertain. In the current study, toxicity was assessed using both in vitro and in vivo systems to understand a possible mechanism of cell death. Rat Pleural Mesothelial Cells (RPMCs) were exposed to 50-800 μg/ml SiO2 …

Perfluorooctane Sulfonate (Pfos)-Induced Disruption Of Mitochondrial Activity And Cell Adhesion In Liver Cells, Phuong Dam Nam Tran

Graduate Theses/Dissertations

Perfluorooctane sulfonate (PFOS) is a persistent environmental pollutant associated with potential hepatoxic effects and other health risks. Despite its widespread distribution, the mechanisms underlying its toxicities remain to be fully understood. To investigate PFOS toxicology, my study utilized HepG2 and THLE-2 human hepatic cell models to replicate conditions reflecting PFOS accumulation in the liver. Cell viability, cell stress, and cell death assays were conducted to assess the toxicological influence of the chemical on both cell lines. Total RNA extraction was performed, followed by cDNA sequencing, and RT-qPCR. The XTT viability assay revealed a dose-dependent decrease in number of viable cells …

Combination Treatment Of Cordycepin And Radiation Induces Apoptosis Accompanied By Protective Autophagy In Tm3 Mouse Leydig Progenitor Cells, Yu-Yan Lan, Yi-Ping Lee, Wei-Ru Huang, Chun-Ying Yu, Lyh-Jyh Hao, Chun-Hung Lin, Bu-Miin Huang

Journal of Food and Drug Analysis

Leydig cells are anatomically located in the testicular interstitial tissue, and their main function is to produce and secrete testosterone and indirectly support spermatogenesis. We previously reported that the combination treatment of cordycepin and radiation can effectively induce Leydig tumor cell apoptosis through cell cycle arrest, caspase activation, endoplasmic reticulum (ER) stress, reactive oxygen species (ROS) accumulation, and DNA damage. However, there is still a lack of scientific evidence for the susceptibility of normal Leydig cells to the combination treatment. In the present study, mouse TM3 Leydig progenitor cells were used as a model to evaluate the effects and mechanisms …

Investigation Of The Effects Of The Peptidylarginine Deiminase Inhibitor Cl-Amidine On Apoptosis And Gene Expression In Ovarian Cancer, Victoria Walden

Longwood Senior Thesis Proposal

Peptidylarginine deiminases (PADs) are a family of enzymatic proteins responsible for the conversion of arginine and methylarginine residues to citrulline. This conversion is important for several key cellular processes including transcriptional gene regulation. Recently, a link has been established between overexpression of a particular PAD, PAD4, and the accelerated progression of both autoimmune diseases and cancers. Ovarian cancer exhibits heightened levels of PAD4 in affected cells. High levels of PAD4 are associated with the formation of neutrophil extracellular traps (NETs) that promote cancer metastasis, and downregulation of the p53 apoptotic pathway. Thus, it is important to explore inhibitors of PAD4. …

Xanthohumol As A Potential Therapeutic Strategy For Acute Myeloid Leukemia: Targeting The Flt3/Srpk1 Signaling Axis, Duan-Na Zhang, Wen-Ya Yang, Xiao-Xue Hu, Xiao-Min-Ting Song, Chuan-Jie Guo, Fu Peng, Yu-Zhi Li, Zhi-Xing Cao

Journal of Food and Drug Analysis

Xanthohumol (XN) is an isoprene chalcone found in hops (Humulus lupulus L.), a food ingredient with a wide range of pharmacological activities. The aim of this study was to reveal the therapeutic effect of XN on acute myeloid leukemia (AML) and the potential underlying molecular mechanism. Through network pharmacology analysis, molecular docking, and HTRF determination, XN was shown to inhibit the kinase activities of FLT3 and SRPK1 by targeting their ATP-binding domains, with IC₅₀ values of 1.51 ± 0.44 μM and 0.37 ± 0.15 μM, respectively. By inhibiting AML cell proliferation, promoting apoptosis, regulating autophagy, and inhibiting …

Synthetic Nucleoside Labels For Studying Cell-Free Dna, Dibya Guragai

Browse all Theses and Dissertations

Cell-free DNA (cfDNA) can arise from dying cells or be actively secreted by living cells, and is found either unbound, within extracellular vesicles, or in other macromolecular complexes. cfDNA plays roles in intercellular communication and immune responses and is clinically used for diagnostics through PCR and DNA sequencing. Interestingly, our lab has detected lesions in cfDNA after treatment with DNA-damaging agents including UVB and cisplatin. These findings prompted further investigation into which DNA lesions and labels can be found in the cell-free space. Importantly, we sought a mechanism of labeling DNA with a synthetic nucleoside to enable robust tracing using …

The E-Liquid Flavorings Cinnamaldehyde, Vanillin, And Ethyl Vanillin Induce Cellular Stress Responses In Human Proximal Tubule (Hk-2) Epithelial Cells, Ashley J. Cox

Theses, Dissertations and Capstones

The use of electronic nicotine delivery systems (ENDS) has become popular in recent years as an alternative to traditional cigarettes. These devices heat and subsequently vaporize e-liquids for inhalation by the user, which allows for the delivery of ingredients such as flavorings, nicotine, and solvents through the vapor. Flavorings used in e-liquids are “generally recognized as safe” (GRAS) for consumption by the Food and Drug Administration (FDA), however there are currently no recommendations on safety regarding the inhalation of flavoring agents. While research characterizing effects of e-liquids and their flavorings is abundant in lung and respiratory tract models, few studies …

Sensitizing Keap1 Loss Non-Small Cell Lung Cancer To Artesunate Anti-Cancer Activity, Keng Hee Peh

Theses and Dissertations--Pharmacy

Lung cancer is the global leading cause of cancer related death. Non-small cell lung cancer (NSCLC) accounts for 80% of lung cancer diagnoses conferring a significant disease burden. However, certain mutations in tumor suppressors such as Kelch-like ECH-associated protein 1 (KEAP1) confers resistance to standard of care therapy in NSCLC. KEAP1 is known to regulate multiple cellular processes such as oxidative stress response and anti-apoptotic pathways. Furthermore, KEAP1 loss of function in NSCLC is associated with poorer clinical outcomes and there are no currently approved therapies for KEAP1 loss NSCLC and represents an unmet clinical need. Artesunate (Art) demonstrated anti-cancer …

Neurodevelopmental Vulnerability To Gestational Ozone Exposure, Vishnupriya Alavala, Sarah E. Brent, Christopher G. Canal, Joseph Wang, Russell P. Hunter, Matthew J. Campen, Andrew K. Ottens

Undergraduate Research Posters

Ambient air pollution accounts for about 4.2 million premature deaths annually per the World Health Organization. Ozone (O3) is a highly reactive air pollutant found in smog and is implicated in cellular damage leading to organ dysfunction. Ambient air pollution is associated with neurodevelopmental, behavioral, and cognitive disorders though ozone’s role is unknown. Studies here look at ozone exposure shortly after implantation vs. shortly before term to evaluate differences in neurodevelopmental susceptibility over time.

To inquire on the effects of ozone on the fetal brain, pregnant Sprague-Dawley rats were exposed once to 0.3 ppm of O3 or filtered air (FA) …

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

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 …

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 …

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 …

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 …

Subchronic Oral Cylindrospermopsin Exposure Alters The Host Gut Microbiome And Is Associated With Progressive Hepatic Inflammation, Stellate Cell Activation, And Mild Fibrosis In A Preclinical Study, Punnag Saha, Macayla Upright, Dipro Bose, Subhajit Roy, Ayushi Trivedi, Madhura More, Geoff Scott Ph.D., Bryan W. Brooks, Saurabh Chatterjee

Faculty Publications

Epidemiological studies have reported a strong association between liver injury and incidences of hepatocellular carcinoma in sections of humans globally. Several preclinical studies have shown a strong link between cyanotoxin exposure and the development of nonalcoholic steatohepatitis, a precursor of hepatocellular carcinoma. Among the emerging threats from cyanotoxins, new evidence shows cylindrospermopsin release in freshwater lakes. A known hepatotoxin in higher concentrations, we examined the possible role of cylindrospermopsin in causing host gut dysbiosis and its association with liver pathology in a mouse model of toxico-pharmacokinetics and hepatic pathology. The results showed that oral exposure to cylindrospermopsin caused decreased diversity …

Targeting Delivery Of Bcl-2 Family Protein Inhibitor Has The Potential To Treat Cancer And Fibrosis, Mohammad Nurul Huda

Open Access Theses & Dissertations

Apoptosis is a naturally occurring cell death mechanism to remove the selective cell population. B-cell leukemia/lymphoma-2 (BCL-2) family protein plays a critical role in activating the upstream apoptosis signaling pathway, primarily the intrinsic apoptosis pathway. The BCL-2 family consists of both pro-and anti-apoptotic proteins, which are structurally and functionally similar, containing up to four BCL-2 homologies (BH) motifs (BH1-4). Defecting apoptosis along this signaling pathway can lead to various events, including malignant cell transformation, tumor metastasis, tissue fibrosis, and drug resistance. In fibrosis, the aberrant apoptosis signaling also activates multiple effector proteins and growth factors, such as TGF-β, CTGF, and …

Induction Of Mitochondrial-Dependent Apoptosis By Essential Oil Of Toona Sinensis Root Through Akt, Mtor And Nf-Κb Signalling Pathways In Human Renal Cell Carcinoma Cells, Yu-Chi Chen, Chiao-Ling Hsieh, Bu-Miin Huang, Yungchia Chen

Journal of Food and Drug Analysis

Natural products have long been considered as a kind of complementary medicine. In this study, we investigate the apoptotic effect of essential oils of Toona sinensis roots (TSR) on human clear cell renal cell carcinomas (ccRCC). The sesquiterpene content of TSR essential oil was determined via GC/MS analysis. TSR decreased ccRCC cell viabilities, inducing ROS generation and reduction of the mitochondrial membrane potential. Moreover, TSR inhibited Bcl-2 and Hsp90 expression but increased PARP-1 cleavage and cytochrome c release. Akt, mTOR and NF-kB phosphorylation and HIF-a expression were all inhibited, which likely contributed to the anti-proliferative and anti-adhesive effects of TSR.

The Role Of The Cell-Surface Protease Tmprss13 In Colorectal Cancer, Fausto Alexander Varela

Wayne State University Dissertations

Colorectal cancer (CRC) is one of the most common and deadly cancers in both men and women in the United States. Extracellular proteolysis is often dysregulated in cancer including (CRC), resulting in degradation of extracellular matrix, as well as cleavage, processing, or shedding of cell adhesion molecules, growth factors, and cytokines. Several members of the type II transmembrane serine protease (TTSP) family have been shown to play critical roles in cancer progression; however, many family members have not yet been characterized in malignancy. We identified TMPRSS13 transcript to be upregulated in CRC compared to normal colon. This increase was confirmed …

Pyronaridine Exerts Potent Cytotoxicity On Human Breast And Hematological Cancer Cells Through Induction Of Apoptosis, Paulina J. Villanueva, Alberto Martinez, Sarah T. Baca, Rebecca E. Dejesus, Manuel Larragoity, Lisett Contreras, Denisse A. Gutierrez, Armando Varela-Ramirez, Renato J. Aguilera

Publications and Research

The potent antimalarial drug pyronaridine (PND) was tested for its potential as an anticancer drug. After exposing cancerous (17) and non-cancerous (2) cells to PND for 72 hr, PND was found to exhibit consistent and potent cytotoxic activity at low micromolar (μM) concentrations that ranged from 1.6 μM to 9.4 μM. Moreover, PND exerted a significant selective cytotoxicity index (SCI) on five out of seven breast cancer cell lines tested, with favorable values of 2.5 to 4.4, as compared with the non-cancerous breast MCF-10A cell line. By using the same comparison, PND exhibited a significant SCI on three out of …

Role Of Mcp-1 And Ccr2 In Ethanol-Induced Neuroinflammation And Neurodegeneration In The Developing Brain, Kai Zhang, Haiping Wang, Mei Xu, Jacqueline A. Frank, Jia Luo

Pharmacology and Nutritional Sciences Faculty Publications

Background: Neuroinflammation and microglial activation have been implicated in both alcohol use disorders (AUD) and fetal alcohol spectrum disorders (FASD). Chemokine monocyte chemoattractant protein 1 (MCP-1) and its receptor C-C chemokine receptor type 2 (CCR2) are critical mediators of neuroinflammation and microglial activation. FASD is the leading cause of mental retardation, and one of the most devastating outcomes of FASD is the loss of neurons in the central nervous system (CNS). The underlying molecular mechanisms, however, remain unclear. We hypothesize that MCP-1/CCR2 signaling mediates ethanol-induced neuroinflammation and microglial activation, which exacerbates neurodegeneration in the developing brain.

Methods: C57BL/6 mice and …

Loss Of The Na+/H+ Exchange Regulatory Factor 1 Results In Increased Susceptibility To Cisplatin-Induced Acute Kidney Injury., Adrienne M. Bushau-Sprinkle

Electronic Theses and Dissertations

Background. Acute kidney injury (AKI), an abrupt loss of kidney function which carries a high mortality and confers an increased risk of chronic kidney disease, develops in 30% of patients who receive cisplatin, a widely used chemotherapeutic agent [1], [2], [3]. The sodium hydrogen exchange regulatory factor isoform 1 (NHERF1) is a scaffolding protein that anchors multiple membrane proteins, in renal proximal tubules [4]. NHERF-1 deficient mice have aberrant localization of BBM proteins in intracellular compartments [5]. The investigators have recently demonstrated NHERF1 deficient proximal tubule cells have an underlying …

Minocycline Protects Developing Brain Against Ethanol-Induced Damage, Xin Wang, Kai Zhang, Fanmuyi Yang, Zhenhua Ren, Mei Xu, Jacqueline A. Frank, Zun-Ji Ke, Jia Luo

Pharmacology and Nutritional Sciences Faculty Publications

Fetal alcohol spectrum disorders (FASD) are caused by ethanol exposure during the pregnancy and is the leading cause of mental retardation. Ethanol exposure during the development results in the loss of neurons in the developing brain, which may underlie many neurobehavioral deficits associated with FASD. It is important to understand the mechanisms underlying ethanol-induced neuronal loss and develop appropriate therapeutic strategies. One of the potential mechanisms involves neuroimmune activation. Using a third trimester equivalent mouse model of ethanol exposure, we demonstrated that ethanol induced a wide-spread neuroapoptosis, microglial activation, and neuroinflammation in C57BL/6 mice. Minocycline is an antibiotic that inhibits …

Chloroquine-Inducible Par-4 Secretion Is Essential For Tumor Cell Apoptosis And Inhibition Of Metastasis, Ravshan Burikhanov, Nikhil Hebbar, Sunil K. Noothi, Nidhi Shukla, James Sledziona, Nathália Araujo, Meghana Kudrimoti, Qing Jun Wang, David S. Watt, Danny R. Welch, Jodi Maranchie, Akihiro Harada, Vivek M. Rangnekar

Radiation Medicine Faculty Publications

The induction of tumor suppressor proteins capable of cancer cell apoptosis represents an attractive option for the re-purposing of existing drugs. We report that the anti-malarial drug, chloroquine (CQ), is a robust inducer of Par-4 secretion from normal cells in mice and cancer patients in a clinical trial. CQ-inducible Par-4 secretion triggers paracrine apoptosis of cancer cells and also inhibits metastatic tumor growth. CQ induces Par-4 secretion via the classical secretory pathway that requires the activation of p53. Mechanistically, p53 directly induces Rab8b, a GTPase essential for vesicle transport of Par-4 to the plasma membrane prior to secretion. Our findings …

Tenofovir Induced Nephrotoxicity: A Mechanistic Study, Rachel A. Murphy

Theses, Dissertations and Capstones

Tenofovir (TFV) is a reverse transcriptase inhibitor that is approved by the United States Food and Drug Administration (FDA) to treat HIV and chronic Hepatitis B. It has a long half-life, allowing for once a day dosing and is effective in treatment of both naive and experienced patients. It is administered orally as tenofovir disoproxil fumarate (TDF) and is deesterified in plasma to the active drug TFV. However, renal impairment is associated with its use; TFV can induce decreased glomerular filtration rate (GFR) and free calcitriol, renal failure, and Fanconi Syndrome. The exact mechanism of toxicity currently remains unknown, largely …

Binge Ethanol Exposure Causes Endoplasmic Reticulum Stress, Oxidative Stress And Tissue Injury In The Pancreas, Zhenhua Ren, Xin Wang, Mei Xu, Fanmuyi Yang, Jacqueline A. Frank, Zun-Ji Ke, Jia Luo

Pharmacology and Nutritional Sciences Faculty Publications

Alcohol abuse is associated with both acute and chronic pancreatitis. Repeated episodes of acute pancreatitis or pancreatic injury may result in chronic pancreatitis. We investigated ethanol-induced pancreatic injury using a mouse model of binge ethanol exposure. Male C57BL/6 mice were exposed to ethanol intragastrically (5 g/kg, 25% ethanol w/v) daily for 10 days. Binge ethanol exposure caused pathological changes in pancreas demonstrated by tissue edema, acinar atrophy and moderate fibrosis. Ethanol caused both apoptotic and necrotic cell death which was demonstrated by the increase in active caspase-3, caspase-8, cleaved PARP, cleaved CK-18 and the secretion of high mobility group protein …

Thrombospondin 1 Deficiency Ameliorates The Development Of Adriamycin-Induced Proteinuric Kidney Disease, Hasiyeti Maimaitiyiming, Qi Zhou, Shuxia Wang

Pharmacology and Nutritional Sciences Faculty Publications

Accumulating evidence suggests that thrombospondin 1 (TSP1) is an important player in diabetic nephropathy. However, the role of TSP1 in podocyte injury and the development of non-diabetic proteinuric kidney disease is largely unknown. In the current study, by using a well-established podocyte injury model (adriamycin-induced nephropathy mouse model), we examined the contribution of TSP1 to the development of proteinuric kidney disease. We found that TSP1 was up-regulated in the glomeruli, notably in podocytes, in adriamycin injected mice before the onset of proteinuria. ADR treatment also stimulated TSP1 expression in cultured human podocytes in vitro. Moreover, increased TSP1 mediated ADR-induced …

Chronic Ethanol Exposure Enhances The Aggressiveness Of Breast Cancer: The Role Of P38Γ, Mei Xu, Siying Wang, Zhenhua Ren, Jacqueline A. Frank, Xiuwei H. Yang, Zhuo Zhang, Zun-Ji Ke, Xianglin Shi, Jia Luo

Pharmacology and Nutritional Sciences Faculty Publications

Both epidemiological and experimental studies suggest that ethanol may enhance aggressiveness of breast cancer. We have previously demonstrated that short term exposure to ethanol (12–48 hours) increased migration/invasion in breast cancer cells overexpressing ErbB2, but not in breast cancer cells with low expression of ErbB2, such as MCF7, BT20 and T47D breast cancer cells. In this study, we showed that chronic ethanol exposure transformed breast cancer cells that were not responsive to short term ethanol treatment to a more aggressive phenotype. Chronic ethanol exposure (10 days - 2 months) at 100 (22 mM) or 200 mg/dl (44 mM) caused the …

Cross-Talk Between The Tumor Suppressors Par-4 And P53, Tripti Shrestha Bhattarai

Theses and Dissertations--Toxicology and Cancer Biology

This work describes the fascinating interplay between two tumor suppressors Prostate apoptosis response-4 (Par-4) and p53. The guardian of the genome, p53, is frequently mutated in human cancers, and may contribute to therapeutic resistance. However, p53 is intact and functional in normal tissues, and we observed that specific activation of p53 in normal fibroblasts could induce apoptosis selectively in p53-deficient cancer cells. This paracrine apoptotic effect was executed by Par-4 secreted in response to p53 activation. Accordingly, activation of p53 in wild-type mice, but not in p53^-/- or Par-4^-/- mice, caused systemic elevation of Par-4 that induced apoptosis …

Interaction Between Na/ K-Atpase And Bcl-2 Proteins Bclxl And Bak, Tariq M. Alqahtani

Browse all Theses and Dissertations

In silico analysis predicts interaction between the Na/ K-ATPase (NKA) and Bcl-2 protein canonical motifs BH3 and BH1. Such interaction is consistent with NKA inhibition by the benzo-phenanthridine alkaloid chelerythrine (CHE), a BH3 mimetic, in human lens epithelial cells (HLEC). This report establishes proof of concept: co-immuno-precipitation and immuno-colocalization showed unequivocal and direct interaction between NKA and Bcl-2 proteins. Particularly, NKA-antibodies co-immunoprecipitated BclXl and BAK in three different epithelial cell lines, HLECs and A549 lung cancer cells, whereas anti-Bcl-2 antibodies failed to pull down NKA. The molecular mass of the BAK proteins pulled down by antibodies against NKA and BclXl …