Medicine and Health Sciences Commons^™

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

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 5a–d 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 5a–d …

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

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

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

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

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

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 …

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

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 Cln3^Δex7/8 mice. WT/Cln3^Δex7/8 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

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 …

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

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

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. …

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 …

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 …

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 …

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 …

Persistent Hepatic Structural Alterations Following Nanoceria Vascular Infusion In The Rat, Michael T. Tseng, Qiang Fu, Khoua Lor, G. Rafael Fernandez-Botran, Zhong-Bin Deng, Uschi M. Graham, D. Allan Butterfield, Eric A. Grulke, Robert A. Yokel

Chemistry Faculty Publications

Understanding the long-term effects and possible toxicity of nanoceria, a widely utilized commercial metal oxide, is of particular importance as it is poised for development as a therapeutic agent based on its autocatalytic redox behavior. We show here evidence of acute and subacute adverse hepatic responses, after a single infusion of an aqueous dispersion of 85 mg/kg, 30 nm nanoceria into Sprague Dawley rats. Light and electron microscopic evidence of avid uptake of nanoceria by Kupffer cells was detected as early as 1 hr after infusion. Biopersistent nanoceria stimulated cluster of differentiation 3⁺ lymphocyte proliferation that intermingled with nanoceria-containing …

Honokiol Enhances Paclitaxel Efficacy In Multi-Drug Resistant Human Cancer Model Through The Induction Of Apoptosis, Xu Wang, Jonathan J. Beitler, Hong Wang, Michael J. Lee, Wen Huang, Lydia Koenig, Sreenivas Nannapaneni, Arm R. Amin, Michael Bonner, Hyung Ju C. Shin, Zhuo Georgia Chen, Jack L. Arbiser, Dong M. Shin

Pharmaceutical Science and Research

Resistance to chemotherapy remains a major obstacle in cancer therapy. This study aimed to evaluate the molecular mechanism and efficacy of honokiol in inducing apoptosis and enhancing paclitaxel chemotherapy in pre-clinical multi-drug resistant (MDR) cancer models, including lineage-derived human MDR (KB-8-5, KB-C1, KB-V1) and their parental drug sensitive KB-3-1 cancer cell lines. In vitro analyses demonstrated that honokiol effectively inhibited proliferation in KB-3-1 cells and the MDR derivatives (IC₅₀ ranging 3.35±0.13 µg/ml to 2.77±0.22 µg/ml), despite their significant differences in response to paclitaxel (IC₅₀ ranging 1.66±0.09 ng/ml to 6560.9±439.52 ng/ml). Honokiol induced mitochondria-dependent and death receptor-mediated apoptosis in …

Reactive Oxygen Species And Mitochondrial Sensitivity To Oxidative Stress Determine Induction Of Cancer Cell Death By P21, Ionica Masgras, Samantha Carrera, Petra J. De Verdier, Paul Brennan, Aneela Majid, Wan Makhtar, Eugene Tulchinsky, George D. Jones, Igor Roninson, Salvador Macip

Faculty Publications

p21(Waf1/Cip1/Sdi1) is a cyclin-dependent kinase inhibitor that mediates cell cycle arrest. Prolonged p21 up-regulation induces a senescent phenotype in normal and cancer cells, accompanied by an increase in intracellular reactive oxygen species (ROS). However, it has been shown recently that p21 expression can also lead to cell death in certain models. The mechanisms involved in this process are not fully understood. Here, we describe an induction of apoptosis by p21 in sarcoma cell lines that is p53-independent and can be ameliorated with antioxidants. Similar levels of p21 and ROS caused senescence in the absence of significant death in other cancer …

Identification Of A Potent Herbal Molecule For The Treatment Of Breast Cancer, Srinivas Koduru, Srinivasan Sowmyalakshmi, Raj Kumar, Rohini Gomathinayagam, Jürgen Rohr, Chendil Damodaran

Pharmaceutical Sciences Faculty Publications

BACKGROUND: Breast cancer (BCa)-related mortality still remains the second leading cause of cancer-related deaths worldwide. Patients with BCa have increasingly shown resistance and high toxicity to current chemotherapeutic drugs for which identification of novel targeted therapies are required.

METHODS: To determine the effect of PDBD on BCa cells, estrogen-receptor positive (ER+)-MCF-7 and estrogen-receptor negative (ER-)-MDA 231 cells were treated with PDBD and the cell viability, apoptotic, cell cycle, Western blot and Promoter assays were performed.

RESULTS: PDBD inhibits cell viability of ER+ and ER- BCa cells by inducing apoptosis without causing significant toxicity in normal breast epithelial cells. While dissecting …

Antitumour And Antimalarial Activity Of Artemisinin–Acridine Hybrids, Michael Jones, Amy Mercer, Paul Stocks, Louise La Pensee, Rick Cosstick, B. Kevin Park, Miriam Kennedy, Ivo Piantanida, Stephen Ward, Jill Davies, Patrick Bray, Sarah Rawe, Jonathon Baird, Tafadzwa Charidza, Omar Janneh, Paul O'Neill

Articles

Artemisinin–acridine hybrids were prepared and evaluated for their in vitro activity against tumour cell lines and a chloroquine sensitive strain of Plasmodium falciparum. They showed a 2–4-fold increase in activity against HL60, MDA-MB-231 and MCF-7 cells in comparison with dihydroartemisinin (DHA) and moderate antimalarial activity. Strong evidence that the compounds induce apoptosis in HL60 cells was obtained by flow cytometry, which indicated accumulation of cells in the G1 phase of the cell cycle.

A Role For Shps-1/Sirpα In Concanavalin A-Dependent Production Of Mmp-9, Arm R. Amin, M. Helal Uddin Biswas, Takeshi Senga, Gen-Sheng Feng, Reiji Kannagi, Munna L. Agarwal, Michinari Hamaguchi

Pharmaceutical Science and Research

SHPS‐1/SIRPα1 is a transmembrane glycoprotein that belongs to the immunoglobulin (Ig) super family. In the present study, we show that SHPS‐1 strongly associates with Concanavalin A (Con A), a plant lectin obtained from jack beans. Further studies with SHPS‐1 mutants reveal that the extracellular domain of SHPS‐1 containing the Ig sequence is responsible for its association with Con A. Con A treatment induces cross‐linking and multimerization of the SHPS‐1 protein in the plasma membrane, accompanied by its tyrosine phosphorylation and recruitment of SHP‐2. In contrast, Ricinus communis agglutinin (RCA), another lectin obtained from castor bean, does not bind or activate …