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Pharmacy and Pharmaceutical Sciences

Apoptosis

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Full-Text Articles in Medicine and Health Sciences

Stress-Induced Changes In Carf Expression Determine Growth Arrest, Apoptosis, Or Malignant Transformation In Cultured Human Cells: Molecular Evidence And Its Application, Mallika Khurana, Rajkumar Singh Kalra, Anupama Chaudhary, Amr Omar, Xiaoshuai Li, Sunil C. Kaul, Renu Wadhwa Sep 2023

Stress-Induced Changes In Carf Expression Determine Growth Arrest, Apoptosis, Or Malignant Transformation In Cultured Human Cells: Molecular Evidence And Its Application, Mallika Khurana, Rajkumar Singh Kalra, Anupama Chaudhary, Amr Omar, Xiaoshuai Li, Sunil C. Kaul, Renu Wadhwa

Research Symposium

Background: CARF (Collaborator of ARF)/CDKN2AIP is an essential protein, first cloned as a binding partner of ARF. It was subsequently shown to interact with p53, HDM2 proteins and regulate growth arrest and apoptosis by its multimodal mechanism of action. Over-expression of CARF caused senescence like growth arrest of cells, its knock-down triggered apoptosis. Intriguingly, malignantly transformed cells showed high level of CARF expression. Based on these findings, we hypothesized that level of CARF expression may be a key determinant of cell proliferation fates; where an increase in its levels causes growth arrest/senescence, but beyond a threshold it activates carcinogenesis.

Methods: …


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 …


Atherosclerosis Preventive Effects Of Marrubiin Against (Tnf-Α)-Induced Oxidative Stress And Apoptosis, Ailar Nakhlband, Alireza Garjani, Nazli Saeedi, Yadollah Omidi, Samad Ghaffari, Jaleh Barar, Morteza Eskandani Sep 2023

Atherosclerosis Preventive Effects Of Marrubiin Against (Tnf-Α)-Induced Oxidative Stress And Apoptosis, Ailar Nakhlband, Alireza Garjani, Nazli Saeedi, Yadollah Omidi, Samad Ghaffari, Jaleh Barar, Morteza Eskandani

HPD Articles

Introduction: Atherosclerosis is a complicated cascade of inflammatory processes, oxidative stress, and apoptosis, making it the most prevalent cardiovascular disease. The onset and progression of cardiovascular diseases are greatly influenced by oxidative stress. Targeting oxidative stress is an effective strategy for treating such diseases. Marrubiin is a bioactive furan labdane diterpenoid acts as a strong antioxidant to protect against oxidative damage. This study aimed to investigate the protective effects of marrubiin against oxidative stress and apoptosis in a cellular model of the vascular system. Methods: Human umbilical vein endothelial cells were treated with varying concentration of marrubiin and its IC50 …


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 …


The Combination Of Cucurbitacin B And Evodiamine Induces Apoptosis And Inhibits Cell Propagation In Glioma Cells, Vrutti Vikasbhai Mehta Jan 2023

The Combination Of Cucurbitacin B And Evodiamine Induces Apoptosis And Inhibits Cell Propagation In Glioma Cells, Vrutti Vikasbhai Mehta

Selected Full-Text Master Theses 2021-

Background

Glioblastoma Multiform (GBM) is a lethal brain tumor. Despite aggressive treatment, the median survival time is 6 to 18 months. These malignant astrocytic tumors exhibit a high proliferation rate and acquire resistance against many existing therapeutic regimens. Temozolomide is a first line chemotherapeutic treatment prescribed along with surgery and radiation but due to the high resistance to the drug and a low patient survival rate, new drugs and drug combinations must continue to be investigated and developed. GBM cells like any cancer cells avoid differentiation and apoptosis. Thus, the induction of differentiation and apoptosis in glioblastoma cells may be …


Carum Carvi Modulates Acetaminophen-Induced Hepatotoxicity: Effects On Tnf-Α, Nf-Κb, And Caspases, Tahir Maqbool Mir, Muneeb U. Rehman, Mohammad Khalid Ashfaq, Wajhul Qamar Nov 2022

Carum Carvi Modulates Acetaminophen-Induced Hepatotoxicity: Effects On Tnf-Α, Nf-Κb, And Caspases, Tahir Maqbool Mir, Muneeb U. Rehman, Mohammad Khalid Ashfaq, Wajhul Qamar

Faculty and Student Publications

Carum carvi is a well-known herb traditionally used as a spice in Asian countries. Acetaminophen is a known marketed drug mainly used as an analgesic. It has been scientifically proven that consumption of acetaminophen (paracetamol) is associated with liver toxicity if taken in high doses without medical supervision. The present study evaluated the in vivo antioxidant and hepatoprotective efficacy of Carum carvi against acetaminophen-induced hepatotoxicity in Wistar rats. Our results demonstrate that Carum carvi, at doses (mg/kg) of 100 (D1) and 200 (D2), showed inhibitory properties for DNA-sugar damage, lipid peroxidation, DPPH scavenging, and increased reducing potential in a concentration-dependent …


Cytotoxic Activity Of Non-Specific Lipid Transfer Protein (Nsltp1) From Ajwain (Trachyspermum Ammi) Seeds, Saud O. Alshammari, Taibah Aldakhil, Qamar A. Alshammari, David Salehi, Aftab Ahmed May 2022

Cytotoxic Activity Of Non-Specific Lipid Transfer Protein (Nsltp1) From Ajwain (Trachyspermum Ammi) Seeds, Saud O. Alshammari, Taibah Aldakhil, Qamar A. Alshammari, David Salehi, Aftab Ahmed

Pharmacy Faculty Articles and Research

Background

Trachyspermum ammi, commonly known as Ajwain, is a member of the Apiaceae family. It is a therapeutic herbal spice with diverse pharmacological properties, used in traditional medicine for various ailments. However, all previous studies were conducted using small molecule extracts, leaving the protein’s bioactivity undiscovered.

Aim

The current study aimed to demonstrate the cytotoxic activity of Ajwain non-specific lipid transfer protein (nsLTP1) in normal breast (MCF10A), breast cancer (MCF-7), and pancreatic cancer (AsPC-1) cell lines. Also, to evaluate its structural stability in human serum as well as at high temperature conditions.

Methods

The cytotoxic activity of Ajwain nsLTP1 was …


Indocyanine-Type Infrared-820 Encapsulated Polymeric Nanoparticle-Assisted Photothermal Therapy Of Cancer, Ramesh Marasini, Santosh Aryal Mar 2022

Indocyanine-Type Infrared-820 Encapsulated Polymeric Nanoparticle-Assisted Photothermal Therapy Of Cancer, Ramesh Marasini, Santosh Aryal

Pharmacy Faculty Publications and Presentations

Organic small-molecule photosensitizers are well-characterized and known for the light-responsive treatment modality including photodynamic therapy. Compared with ultraviolet−visible (UV−vis) light used in conventional photodynamic therapy with organic photosensitizers, near-infrared (NIR) light from 700 to 900 nm is less absorbed and scattered by biological tissue such as hemoglobin, lipids, and water, and thus, the use of NIR excitation can greatly increase the penetration depth and emission. Additionally, NIR light has lower energy than UV−vis that can be beneficial due to less activation of fluorophores present in tissues upon NIR irradiation. However, the low water stability, nonspecific distribution, and short circulation halflife …


Discovery Of New 1h-Pyrazolo[3,4-D]Pyrimidine Derivatives As Anticancer Agents Targeting EgfrWt And EgfrT790m, Ahmed A. Gaber, Mohamed Sobhy, Abdallah Turky, Hanan Gaber Abdulwahab Jan 2022

Discovery Of New 1h-Pyrazolo[3,4-D]Pyrimidine Derivatives As Anticancer Agents Targeting EgfrWt And EgfrT790m, Ahmed A. Gaber, Mohamed Sobhy, Abdallah Turky, Hanan Gaber Abdulwahab

Faculty and Student Publications

New 1H-pyrazolo[3,4-d]pyrimidine derivatives were designed and synthesised to act as epidermal growth factor receptor inhibitors (EGFRIs). The synthesised derivatives were assessed for their in vitro anti-proliferative activities against A549 and HCT-116 cancer cells. Compounds 8, 10, 12a, and 12b showed potent anti-proliferative activities. Compound 12b was the most promising member with IC50 values of 8.21 and 19.56 µM against A549 and HCT-116, respectively. Compounds 8, 10, 12a, and 12b were evaluated for their kinase inhibitory activities against wild EGFR (EGFRWT). Compound 12b was the most potent member showing an IC50 value of 0.016 µM. In addition, compound 12b showed noticeable …


Mcl-1 Inhibition: Managing Malignancy In Multiple Myeloma., Omar Al-Odat, Max Von Suskil, Robert Chitren, Weam Elbezanti, Sandeep Srivastava, Tulin Budak-Alpddogan, Subash C. Jonnalagadda, Bharat Aggarwal, Manoj Pandey Jul 2021

Mcl-1 Inhibition: Managing Malignancy In Multiple Myeloma., Omar Al-Odat, Max Von Suskil, Robert Chitren, Weam Elbezanti, Sandeep Srivastava, Tulin Budak-Alpddogan, Subash C. Jonnalagadda, Bharat Aggarwal, Manoj Pandey

Faculty Scholarship for the College of Science & Mathematics

Multiple myeloma (MM) is a plasma cells neoplasm. The overexpression of Bcl-2 family proteins, particularly myeloid cell leukemia 1 (Mcl-1), plays a critical role in the pathogenesis of MM. The overexpression of Mcl-1 is associated with drug resistance and overall poor prognosis of MM. Thus, inhibition of the Mcl-1 protein considered as a therapeutic strategy to kill the myeloma cells. Over the last decade, the development of selective Mcl-1 inhibitors has seen remarkable advancement. This review presents the critical role of Mcl-1 in the progression of MM, the most prominent BH3 mimetic and semi-BH3 mimetic that selectively inhibit Mcl-1, and …


Cis-Trimethoxystilbene, Exhibits Higher Genotoxic And Antiproliferative Effects Than Its Isomer Trans-Trimethoxystilbene In Mcf-7 And Mcf-10a Cell Lines, Natália Dos Santos Gonçalves, Tamires Maria Silva Pereira De Mello, Cássia Suemi Mizuno, Saqlain Haider Jan 2021

Cis-Trimethoxystilbene, Exhibits Higher Genotoxic And Antiproliferative Effects Than Its Isomer Trans-Trimethoxystilbene In Mcf-7 And Mcf-10a Cell Lines, Natália Dos Santos Gonçalves, Tamires Maria Silva Pereira De Mello, Cássia Suemi Mizuno, Saqlain Haider

Faculty and Student Publications

Stilbenes are a class of natural compounds with a wide variety of biological effects, such as antitumor activity. The best-known stilbene is resveratrol, whose clinical application is limited due to its low bioavailability. Methoxylated derivatives of this stilbene, including cis-trimethoxystilbene (cis-TMS) and trans-trimethoxystilbene (trans-TMS) have demonstrated more pronounced cytotoxic and anti-proliferative effects than resveratrol. Thus, the objective of this study is to evaluate and compare the cytotoxicity and antiproliferative effects of cis-and trans-TMS in MCF-7 and its normal counterpart MCF-10A. Both compounds were cytotoxic, genotoxic, and induced G2-M accumulation and cell death in the two cell lines. These results suggested …


Sulforaphane Protects Against Ethanol-Induced Apoptosis And Teratogenesis Through Epigenetic Modulation Of Anti-Apoptotic Genes., Yihong Li May 2020

Sulforaphane Protects Against Ethanol-Induced Apoptosis And Teratogenesis Through Epigenetic Modulation Of Anti-Apoptotic Genes., Yihong Li

Electronic Theses and Dissertations

Background. Ethanol-induced excessive apoptosis in neural crest cells (NCCs), a multipotent progenitor cell population, is one of the major mechanisms underlying the pathogenesis of Fetal Alcohol Spectrum Disorders (FASD). However, the molecular mechanisms underlying FASD that results from maternal alcohol exposure during pregnancy are poorly understood. The overall goals of this study are to examine the mechanisms by which ethanol induces apoptosis and malformations in vitro and in vivo, and to develop a nutritional-based approach by using SFN and SFN-rich BSE to prevent FASD through epigenetic modulation. Results. This study demonstrates that ethanol exposure resulted in a significant increase …


Antiproliferative And Apoptotic Effects Of Proteins From Black Seeds (Nigella Sativa) On Human Breast Mcf-7 Cancer Cell Line, Yamna Khursid, Basir Syed, Shabana U. Simjee, Obaid Beg, Aftab Ahmed Jan 2020

Antiproliferative And Apoptotic Effects Of Proteins From Black Seeds (Nigella Sativa) On Human Breast Mcf-7 Cancer Cell Line, Yamna Khursid, Basir Syed, Shabana U. Simjee, Obaid Beg, Aftab Ahmed

Pharmacy Faculty Articles and Research

Background

Nigella sativa (NS), a member of family Ranunculaceae is commonly known as black seed or kalonji. It has been well studied for its therapeutic role in various diseases, particularly cancer. Literature is full of bioactive compounds from NS seed. However, fewer studies have been reported on the pharmacological activity of proteins. The current study was designed to evaluate the anticancer property of NS seed proteins on the MCF-7 cell line.

Methods

NS seed extract was prepared in phosphate-buffered saline (PBS), and proteins were precipitated using 80% ammonium sulfate. The crude seed proteins were partially purified using gel filtration …


Exogenous Flupirtine As Potential Treatment For Cln3 Disease, Katia Maalouf, Joelle Makoukji, Sara Saab, Nadine J. Makhoul, Angelica V. Carmona, Nihar Kinarivala, Noël Ghanem, Paul C. Trippier, Rose-Mary Boustany Jan 2020

Exogenous Flupirtine As Potential Treatment For Cln3 Disease, Katia Maalouf, Joelle Makoukji, Sara Saab, Nadine J. Makhoul, Angelica V. Carmona, Nihar Kinarivala, Noël Ghanem, Paul C. Trippier, Rose-Mary Boustany

Journal Articles: Pharmaceutical Sciences

CLN3 disease is a fatal neurodegenerative disorder affecting children. Hallmarks include brain atrophy, accelerated neuronal apoptosis, and ceramide elevation. Treatment regimens are supportive, highlighting the importance of novel, disease-modifying drugs. Flupirtine and its new allyl carbamate derivative (compound 6) confer neuroprotective effects in CLN3-deficient cells. This study lays the groundwork for investigating beneficial effects in Cln3Δex7/8 mice. WT/Cln3Δex7/8 mice received flupirtine/compound 6/vehicle for 14 weeks. Short-term effect of flupirtine or compound 6 was tested using a battery of behavioral testing. For flupirtine, gene expression profiles, astrogliosis, and neuronal cell counts were determined. Flupirtine improved neurobehavioral parameters in …


Luteolin Decreases Egfr-Mediated Cell Proliferation And Induces Apoptosis In Glioblastoma Cell Lines., David M. Anson, Rachel M. Wilcox, Eric Huseman, Trevor Stump, Robert L. Paris, Belinda O. Darkwah, Stacy Lin, Andrea O Adegoke, Rebecca J. Gryka, Denise Simpson, Samson Amos Jun 2018

Luteolin Decreases Egfr-Mediated Cell Proliferation And Induces Apoptosis In Glioblastoma Cell Lines., David M. Anson, Rachel M. Wilcox, Eric Huseman, Trevor Stump, Robert L. Paris, Belinda O. Darkwah, Stacy Lin, Andrea O Adegoke, Rebecca J. Gryka, Denise Simpson, Samson Amos

Pharmaceutical Sciences Faculty Publications

Glioblastomas are a subtype of gliomas, which are the most aggressive and deadly form of brain tumours. The epidermal growth factor receptor (EGFR) is over-expressed and amplified in glioblastomas. Luteolin is a common bioflavonoid found in a variety of fruits and vegetables. The aim of the present study was to explore the molecular and biological effects of luteolin on EGF-induced cell proliferation and the potential of luteolin to induce apoptosis in glioblastoma cells. In vitro cell viability assays demonstrated that luteolin decreased cell proliferation in the presence or absence of EGF. Immunoblots revealed that luteolin decreased the protein expression levels …


Investigations On Cancer Cell Biological Effects Of Cdk8 Inhibitor Q-12, Zhixin Lu Jan 2018

Investigations On Cancer Cell Biological Effects Of Cdk8 Inhibitor Q-12, Zhixin Lu

University of the Pacific Theses and Dissertations

Over the past two decades, protein kinases have been intensively investigated as targets to treat neoplastic diseases. Many protein kinase inhibitors not only have therapeutic potential but are becoming invaluable reagents for the study of cell signaling.

We aspired to use our Cyclin-Dependent Kinase 8 inhibitor, Q-12, as a probe for biomarker discovery for CDK8 inhibitor sensitive tumor types. Q-12 shows potent inhibition of cell viability and induction of apoptosis process in some triple-negative breast cancer and colorectal cancer cell lines in vitro. Western blot results indicate that the reduction of STAT1 phosphorylation could be a robust indicator of CDK8 …


Loss Of Fructose-1,6-Bisphosphatase Induces Glycolysis And Promotes Apoptosis Resistance Of Cancer Stem-Like Cells: An Important Role In Hexavalent Chromium-Induced Carcinogenesis, Jin Dai, Yanli Ji, Wei Wang, Donghern Kim, Leonard Yenwong Fai, Lei Wang, Jia Luo, Zhuo Zhang Sep 2017

Loss Of Fructose-1,6-Bisphosphatase Induces Glycolysis And Promotes Apoptosis Resistance Of Cancer Stem-Like Cells: An Important Role In Hexavalent Chromium-Induced Carcinogenesis, Jin Dai, Yanli Ji, Wei Wang, Donghern Kim, Leonard Yenwong Fai, Lei Wang, Jia Luo, Zhuo Zhang

Toxicology and Cancer Biology Faculty Publications

Hexavalent chromium (Cr(VI)) compounds are confirmed human carcinogens for lung cancer. Our previous studies has demonstrated that chronic exposure of human bronchial epithelial BEAS-2B cells to low dose of Cr(VI) causes malignant cell transformation. The acquisition of cancer stem cell-like properties is involved in the initiation of cancers. The present study has observed that a small population of cancer stem-like cells (BEAS-2B-Cr-CSC) exists in the Cr(VI)-transformed cells (BEAS-2B-Cr). Those BEAS-2B-Cr-CSC exhibit extremely reduced capability of generating reactive oxygen species (ROS) and apoptosis resistance. BEAS-2B-Cr-CSC are metabolic inactive as evidenced by reductions in oxygen consumption, glucose uptake, ATP production, and lactate …


Evaluation Of The Anticancer Activity Of Bioactive Fraction G Extracted From Pavetta Crassipes In Malignant Brain Tumor Cell Lines, Rachel M. Wilcox, Eric Huseman, Stacy Lin, Belinda O. Darkwah, M. O. Emeje, K. S. Gamaniel, A. Orisadipe, N. Enwerem, B. A. Kefas, Rebecca J. Gryka, Denise Simpson, Samson Amos Aug 2017

Evaluation Of The Anticancer Activity Of Bioactive Fraction G Extracted From Pavetta Crassipes In Malignant Brain Tumor Cell Lines, Rachel M. Wilcox, Eric Huseman, Stacy Lin, Belinda O. Darkwah, M. O. Emeje, K. S. Gamaniel, A. Orisadipe, N. Enwerem, B. A. Kefas, Rebecca J. Gryka, Denise Simpson, Samson Amos

Pharmaceutical Sciences Faculty Publications

Objective: Natural products have served as sources of lead compounds that are commonly used in the treatment of human diseases including cancer. Pavetta crassipes has been widely demonstrated to have ethnopharmacological potential in the management of malaria, gastrointestinal conditions, central nervous system behavioral disorders, hypertension, and cancer. The goal of our study was to evaluate the biological and molecular effects of Fraction G, obtained from the plant Pavetta crassipes, on glioblastoma invasive growth and survival.

Methodology: The antiproliferative effects of Fraction G, obtained from Pavetta crassipes, was evaluated using the trypan blue exclusion, (3-(4, 5-Dimethylthiazol- 2yl)-2, 5-Diphenyltetrazolium Bromide; MTT), and …


The Antiproliferative And Apoptotic Effects Of Apigenin On Glioblastoma Cells, Trevor Stump, Brittany Santee, Lauren P. Williams, Rachel Kunze, Chelsae Heinze, Eric Huseman, Rebecca J. Gryka, Denise Simpson, Samson Amos Jul 2017

The Antiproliferative And Apoptotic Effects Of Apigenin On Glioblastoma Cells, Trevor Stump, Brittany Santee, Lauren P. Williams, Rachel Kunze, Chelsae Heinze, Eric Huseman, Rebecca J. Gryka, Denise Simpson, Samson Amos

Pharmaceutical Sciences Faculty Publications

OBJECTIVES: Glioblastoma (GBM) is highly proliferative, infiltrative, malignant and the most deadly form of brain tumour. The epidermal growth factor receptor (EGFR) is overexpressed, amplified and mutated in GBM and has been shown to play key and important roles in the proliferation, growth and survival of this tumour. The goal of our study was to investigate the antiproliferative, apoptotic and molecular effects of apigenin in GBM.

METHODS: Proliferation and viability tests were carried out using the trypan blue exclusion, MTT and lactate dehydrogenase (LDH) assays. Flow cytometry was used to examine the effects of apigenin on the cell cycle check-points. …


Tenofovir Induced Nephrotoxicity: A Mechanistic Study, Rachel A. Murphy Jan 2017

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 …


Antitumor Activity Of 2,9-Di-Sec-Butyl-1,10-Phenanthroline, Dongsheng Wang, Shifang Peng, Arm R. Amin, Mohammad Aminur Rahman, Sreenivas Nannapaneni, Yuan Liu, Dong M. Shin, Nabil F. Saba, Jack F. Eichler, Zhuo G. Chen Dec 2016

Antitumor Activity Of 2,9-Di-Sec-Butyl-1,10-Phenanthroline, Dongsheng Wang, Shifang Peng, Arm R. Amin, Mohammad Aminur Rahman, Sreenivas Nannapaneni, Yuan Liu, Dong M. Shin, Nabil F. Saba, Jack F. Eichler, Zhuo G. Chen

Pharmaceutical Science and Research

The anti-tumor effect of a chelating phen-based ligand 2,9-di-sec-butyl-1,10-phenanthroline (dsBPT) and its combination with cisplatin were examined in both lung and head and neck cancer cell lines and xenograft animal models in this study. The effects of this agent on cell cycle and apoptosis were investigated. Protein markers relevant to these mechanisms were also assessed. We found that the inhibitory effect of dsBPT on lung and head and neck cancer cell growth (IC50 ranged between 0.1–0.2 μM) was 10 times greater than that on normal epithelial cells. dsBPT alone induced autophagy, G1 cell cycle arrest, and apoptosis. Our in vivo …


The Effect Of Luteolin On Human Glioblastoma, David M. Anson, Samson Amos, Robert L. Paris, Denise S. Simpson Apr 2016

The Effect Of Luteolin On Human Glioblastoma, David M. Anson, Samson Amos, Robert L. Paris, Denise S. Simpson

The Research and Scholarship Symposium (2013-2019)

Glioblastoma multiforme (GBM) is widely recognized as the most common and lethal of the malignant gliomas. Few effective therapeutic treatments are available as five-year survival rates of diagnosed individuals are less than five percent. Luteolin, a common flavonoid found in a variety of fruits and vegetables, has demonstrated significant promise in combating cancers of the breast, colon, liver, lung, and bone. In this study, we investigated the effects of luteolin on glioblastoma multiforme cell lines U-251, U-87, and U-1242. Cell viability was assessed using cell count with trypan blue exclusion and MTT assays. Results revealed that luteolin reduces GBM cell …


Saffron Extract And Its Active Constituents As Preventative And/Or Treatment Agents For Prostate Cancer Using In Vitro And In Vivo Models, Faisal Fayih Albaqami Jan 2016

Saffron Extract And Its Active Constituents As Preventative And/Or Treatment Agents For Prostate Cancer Using In Vitro And In Vivo Models, Faisal Fayih Albaqami

Electronic Theses and Dissertations

Saffron extract and its active constituents were evaluated as chemopreventatives and/or treatments for prostate cancer. Different models of prostate cancer (in vitro and in vivo) were used for studying saffron and its constituents’ mechanisms. In normal prostate cells, saffron extract, crocetin, and safranal, in non-toxic concentrations, possessed antioxidant properties against the reactive oxygen species induced by H2O2 which further supports saffron constituents as chemopreventative agents. Moreover, saffron and its active constituents produced cytotoxicity in prostate cancer cells through intrinsic apoptosis pathways. Potential efficacy in minimizing prostate cancer metastasis was also examined. Saffron extract, crocetin, and safranal decreased the migration and …


Sulfated Dehydropolymer Of Caffeic Acid For Repair Of Lung Damage And Emphysema, Tien M. Truong Jan 2016

Sulfated Dehydropolymer Of Caffeic Acid For Repair Of Lung Damage And Emphysema, Tien M. Truong

Theses and Dissertations

The complex pathobiologic mechanisms of emphysema are not fully understood, leaving this deadly disease without effective pharmacotherapy for a cure. This project hypothesized that the sulfated dehydropolymer of caffeic acid (CDSO3) exhibits Fe2+ chelation-based hypoxia inducible factor-1a (HIF-1a) up-regulatory protective activities against in vitro emphysematous cell death and for in vivo reversal of emphysema induced with SU5416, a vascular endothelial growth factor blocker.

Using in vitro chromogenic competitive inhibition assays, CDSO3 was shown to chelate Fe2+ (IC50 of 23 µM), but not Fe3+ ions. The trypan blue exclusion and lactate

dehydrogenase assays were then employed to …


Feasibility Of Integrating Tripterygium Wilfordii Into Modern Cancer Therapy For Increased Efficacy With Minimal Toxicity, Andy Vo Jan 2016

Feasibility Of Integrating Tripterygium Wilfordii Into Modern Cancer Therapy For Increased Efficacy With Minimal Toxicity, Andy Vo

Auctus: The Journal of Undergraduate Research and Creative Scholarship

Cancer is the second leading cause of death in the U.S., and millions of novel cancer cases are being diagnosed each year. While chemotherapy and ionizing radiation are effective treatments against these malignant tumors, the adverse effects that accompany such treatments are devastating. In order to find alternative treatment methods with less side effects, we turn to Eastern herbal medicine. Recent scientific research has found that Tripterygium wilfordii, an herbal medicine traditionally used to treat inflammation in China, contains compounds (triptolide and celastrol) that prevent the growth of solid tumors, induce apoptosis, and prevent metastasis of developed tumors. Investigations on …


The Regulation And Mechanisms Of Egfr-Mediated Apoptosis In Mda-Mb-468 Cells., Nicole Marion Jackson Aug 2015

The Regulation And Mechanisms Of Egfr-Mediated Apoptosis In Mda-Mb-468 Cells., Nicole Marion Jackson

Electronic Theses and Dissertations

Background: The Epidermal Growth Factor Receptor (EGFR) is a 170- kilodalton transmembrane protein that belongs to the ErbB family of receptor tyrosine kinases. Upon ligand-mediated activation, the EGFR responsible for cell growth, proliferation, and tissue homeostasis in epithelial cells; however, the EGFR is overexpressed in many human malignancies including MDA-MB-468 cells, a metastatic breast epithelial cell line. Previous studies have indicated that within the MDA-MB-468 cell line, receptors at the cell surface promote cell growth when activated with Epidermal Growth Factor (EGF) ligand. Activated receptors that are internalized to the endosomes however induce apoptosis. This contrasting response at different cellular …


Amphiphilic Tobramycin Analogues As Antibacterial And Antifungal Agents, Sanjib K. Shrestha, Marina Y. Fosso, Keith D. Green, Sylvie Garneau-Tsodikova Aug 2015

Amphiphilic Tobramycin Analogues As Antibacterial And Antifungal Agents, Sanjib K. Shrestha, Marina Y. Fosso, Keith D. Green, Sylvie Garneau-Tsodikova

Pharmaceutical Sciences Faculty Publications

In this study, we investigated the in vitro antifungal activities, cytotoxicities, and membrane-disruptive actions of amphiphilic tobramycin (TOB) analogues. The antifungal activities were established by determination of MIC values and in time-kill studies. Cytotoxicity was evaluated in mammalian cell lines. The fungal membrane-disruptive action of these analogues was studied by using the membrane-impermeable dye propidium iodide. TOB analogues bearing a linear alkyl chain at their 6″-position in a thioether linkage exhibited chain length-dependent antifungal activities. Analogues with C12 and C14 chains showed promising antifungal activities against tested fungal strains, with MIC values ranging from 1.95 to 62.5 mg/liter …


Initial Evidence Of Endothelial Cell Apoptosis As A Mechanism Of Systemic Capillary Leak Syndrome, Ragheb Assaly, Dan Olson, Jeffrey Hammersley, Pan-Sheng Fan, Jiang Liu, Joseph Shapiro, M. Kahaleh Jul 2015

Initial Evidence Of Endothelial Cell Apoptosis As A Mechanism Of Systemic Capillary Leak Syndrome, Ragheb Assaly, Dan Olson, Jeffrey Hammersley, Pan-Sheng Fan, Jiang Liu, Joseph Shapiro, M. Kahaleh

Jiang Liu

Background: Systemic capillary leak syndrome (SCLS) is a rare disorder of unknown etiology that is characterized by acute recurrent attacks of hypovolemic shock commonly following an inflammatory stimulus such as a viral illness. Prophylactic therapy is generally ineffective, and the outcome is frequently fatal. Methods: In order to investigate the cellular mechanisms leading to SCLS, we examined the effects of sera from two patients with active SCLS on microvascular endothelial cell apoptosis in vitro. Apoptosis was determined by morphologic criteria, DNA fragmentation, annexin V stain, and by a quantitative photometric assay. The apoptotic pathway was investigated by Western blot of …


Curcumin Induces Apoptosis Of Upper Aerodigestive Tract Cancer Cells By Targeting Multiple Pathways, Arm R. Amin, A. Haque, M. A. Rahman, Z. G. Chen, F. R. Khuri, D. M. Shin Apr 2015

Curcumin Induces Apoptosis Of Upper Aerodigestive Tract Cancer Cells By Targeting Multiple Pathways, Arm R. Amin, A. Haque, M. A. Rahman, Z. G. Chen, F. R. Khuri, D. M. Shin

Pharmaceutical Science and Research

Curcumin, a natural compound isolated from the Indian spice "Haldi" or "curry powder", has been used for centuries as a traditional remedy for many ailments. Recently, the potential use of curcumin in cancer prevention and therapy urges studies to uncover the molecular mechanisms associated with its anti-tumor effects. In the current manuscript, we investigated the mechanism of curcumin-induced apoptosis in upper aerodigestive tract cancer cell lines and showed that curcumin-induced apoptosis is mediated by the modulation of multiple pathways such as induction of p73, and inhibition of p-AKT and Bcl-2. Treatment of cells with curcumin induced both p53 and the …


Feasibility Of Integrating Tripterygium Wilfordii Into Modern Cancer Therapy For Increased Efficacy And Minimal Toxicity, Ngoc T. Vo Jan 2015

Feasibility Of Integrating Tripterygium Wilfordii Into Modern Cancer Therapy For Increased Efficacy And Minimal Toxicity, Ngoc T. Vo

Undergraduate Research Posters

Cancer is the second leading cause of death in the U.S. and millions of novel cancer cases are being diagnosed each year. While chemotherapy and ionizing radiation are effective treatments against these malignant tumors, the adverse effects that accompany such treatments are devastating. In order to find alternative treatment methods with less side effects, we turn to Eastern herbal medicine. Recent scientific research has found that Tripterygium wilfordii, an herbal medicine traditionally used to treat inflammation in China, contains compounds (triptolide and celastrol) that prevent the growth of solid tumors, induce apoptosis, and prevent metastasis of developed tumors. Investigations …