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Full-Text Articles in Pharmacology, Toxicology and Environmental Health
Use Of Small Molecule Fanconi Anemia Pathway Inhibitors As Sensitizing Agents To Laromustine., Sam W. Marchant
Use Of Small Molecule Fanconi Anemia Pathway Inhibitors As Sensitizing Agents To Laromustine., Sam W. Marchant
Honors Theses
Laromustine is an experimental chemotherapeutic sulfonyl hydrazine prodrug shown in clinical trials to be effective against acute myeloid leukemia. The mechanism of action of laromustine involves interstrand crosslinking, via chloroethylation, and enzyme inhibition, caused by carbamoylation. The work described herein aims to investigate whether inhibition of the replication-dependent interstrand crosslink repair Fanconi Anemia pathway further sensitizes cells to laromustine. By measuring metabolic activity immediately after drug exposure, we find laromustine to be equally as cytotoxic towards Fanconi Anemia deficient and wild type cells. However, through clonogenic assays we show Fanconi Anemia mutations sensitize cells to laromustine’s anti-proliferative effect. Furthermore, we …
B7h6: A Cancer Biomarker For The Development Of Novel Immunotherapy Approaches, Mariana Phillips
B7h6: A Cancer Biomarker For The Development Of Novel Immunotherapy Approaches, Mariana Phillips
Seton Hall University Dissertations and Theses (ETDs)
Cancer-based immunotherapy has led the evolution of biologics that can stimulate immune responses towards tumor eradication. The synthesis of small to intermediate size molecules with the targeting and effector functions of mAb may represent a novel class of immunotherapeutics that may overcome the limitations of their biological counterparts.Towards this objective, B7H6 has been identified as a protein ligand localized on the cell surface of transformed tumor cells. B7H6 binds specifically to the activating receptor NKp30, constitutively expressed on all resting and active NK cells. Upon ligand:receptor binding, B7H6 triggers NK cell activation and release of chemokines and pro-inflammatory cytokines such …
Increased Geranylgeranylated K-Ras Contributes To Antineoplastic Effects Of Farnesyltransferase Inhibitors., Mandy A. Hall
Increased Geranylgeranylated K-Ras Contributes To Antineoplastic Effects Of Farnesyltransferase Inhibitors., Mandy A. Hall
Dissertations & Theses (Open Access)
The Ras family of small GTPases (N-, H-, and K-Ras) is a group of important signaling mediators. Ras is frequently activated in some cancers, while others maintain low level activity to achieve optimal cell growth. In cells with endogenously low levels of active Ras, increasing Ras signaling through the ERK and p38 MAPK pathways can cause growth arrest or cell death. Ras requires prenylation – the addition of a 15-carbon (farnesyl) or 20-carbon (geranylgeranyl) group – to keep the protein anchored into membranes for effective signaling. N- and K-Ras can be alternatively geranylgeranylated (GG’d) if farnesylation is inhibited but are …
Clausena Excavata Burm. F. (Rutaceae): A Review Of Its Traditional Uses, Pharmacological And Phytochemical Properties., Dr Syam Mohan
Clausena Excavata Burm. F. (Rutaceae): A Review Of Its Traditional Uses, Pharmacological And Phytochemical Properties., Dr Syam Mohan
Syam Mohan
The present review describes the morphological, traditional, phytochemical and pharmacological aspects of Clausena excavata (Burm. f., Rutaceae). The plant grows wild in the tropical and subtropical parts of Asia and represents one of the richest sources of medicinal natural products. It is intensively used currently in traditional medicine for treatment of different illnesses. One part or a mixture of two or more parts of the plant in the form of powder or liquid doze is usually given to the patient. Phytochemically, many pure compounds from several secondary metabolite groups of C. excavata have been isolated from different parts of the …
Chloroform Fraction Of Centratherum Anthelminticum (L.) Seed Inhibits Tumor Necrosis Factor Alpha And Exhibits Pleotropic Bioactivities: Inhibitory Role In Human Tumor Cells, Dr Syam Mohan
Syam Mohan
We investigated the antioxidant potential, cytotoxic effect, and TNF-α inhibition activity with NF-κB activation response in a chloroformfraction of Centratherum anthelminticum seeds (CACF). The antioxidant property of CACF was evaluated with DPPH, ORAC, and FRAP assays, which demonstrated significant antioxidant activity. The cytotoxicity of CACF was tested using theMTT assay; CACF effective inhibitory concentrations (IC50) for A549, PC-3, MCF-7, and WRL-68 cells were 31.42 ± 5.4, 22.61 ± 1.7, 8.1±0.9, and 54.93±8.3 μg/mL, respectively. CACF effectively and dose-dependently inhibited TNF-α release, in vitro and in vivo. CACF inhibited TNF-α secretion in stimulated RAW264.7macrophage supernatants with an IC50 of 0.012 μg/mL, …
In Vitro Anti-Inflammatory, Cytotoxic And Antioxidant Activities Of Boesenbergin A, A Chalcone Isolated From Boesenbergia Rotunda (L.) (Fingerroot), Dr Syam Mohan
Syam Mohan
The current in vitro study was designed to investigate the anti-inflammatory, cytotoxic and antioxidant activities of boesenbergin A (BA), a chalcone derivative of known structure isolated from Boesenbergia rotunda. Human hepatocellular carcinoma (HepG2), colon adenocarcinoma (HT-29), non-small cell lung cancer (A549), prostate adenocarcinoma (PC3), and normal hepatic cells (WRL-68) were used to evaluate the cytotoxicity of BA using the MTT assay. The antioxidant activity of BA was assessed by the ORAC assay and compared to quercetin as a standard reference antioxidant. ORAC results are reported as the equivalent concentration of Trolox that produces the same level of antioxidant activity as …
Synthesis Of Chalcones With Anticancer Activities., Dr Syam Mohan
Synthesis Of Chalcones With Anticancer Activities., Dr Syam Mohan
Syam Mohan
Several chalcones were synthesized and their in vitro cytotoxicity against various human cell lines, including human breast adenocarcinoma cell line MCF-7, human lung adenocarcinoma cell line A549, human prostate cancer cell line PC3, human adenocarcinoma cell line HT-29 (colorectal cancer) and human normal liver cell line WRL-68 was evaluated. Most of the compounds being active cytotoxic agents, four of them with minimal IC50 values were chosen and studied in detail with MCF-7 cells. The compounds 1, 5, 23, and 25 were capable in eliciting apoptosis in MCF-7 cells as shown by multiparameter cytotoxicity assay and caspase-3/7, -8, and -9 activities …
Cucurbitacin L 2-O- Glucoside Demonstrates Apoptogenesis In Colon Adenocarcinoma Cells (Ht-29): Involvement Of Reactive Oxygen And Nitrogen Species Regulation, Dr Syam Mohan
Syam Mohan
Emerging evidence suggests that reactive oxygen (ROS) and nitrogen (RNS) species can contribute to diverse signalling pathways of inflammatory and tumour cells. Cucurbitacins are a group of highly oxygenated triterpenes. Many plants used in folk medicine to treat cancer have been found to contain cucurbitacins displaying potentially important anti-inflammatory actions. The current study was designed to investigate the anti-ROS and -RNS effects of cucurbitacin L 2-O-β-glucoside (CLG) and the role of these signaling factors in the apoptogenic effects of CLG on human colon cancer cells (HT-29). This natural cucurbitacin was isolated purely from Citrullus lanatus var. citroides (Cucurbitaceae). The results …
Dentatin Induces Apoptosis In Prostate Cancer Cells Via Bcl-2, Bcl-Xl, Survivin Downregulation, Caspase-9, -3/7 Activation And Nf-Kb Inhibition., Dr Syam Mohan
Syam Mohan
This study was set to investigate antiproliferative potential of dentatin (a natural coumarin isolated from Clausena excavata Burm. F) against prostate cancer and to delineate the underlying mechanism of action. Treatment with dentatin dose-dependently inhibited cell growth of PC-3 and LNCaP prostate cancer cell lines, whereas it showed less cytotoxic effects on normal prostate epithelial cell line (RWPE-1). The inhibitory effect of dentatin on prostate cancer cell growth was due to induction of apoptosis as evidenced by Annexin V staining and cell shrinkage. We found that dentatin-mediated accumulation of reactive oxygen species (ROS) and downregulated expression levels of antiapoptotic molecules …
The Growth Suppressing Effects Of Girinimbine On Hepg2 Involve Induction Of Apoptosis And Cell Cycle Arrest, Syam Mohan
The Growth Suppressing Effects Of Girinimbine On Hepg2 Involve Induction Of Apoptosis And Cell Cycle Arrest, Syam Mohan
Syam Mohan
Murraya koenigii is an edible herb widely used in folk medicine. Here we report that girinimbine, a carbazole alkaloid isolated from this plant, inhibited the growth and induced apoptosis in human hepatocellular carcinoma, HepG2 cells. The MTT and LDH assay results showed that girinimbine decreased cell viability and increased cytotoxicity in a dose-and time-dependent manner selectively. Girinimbine-treated HepG2 cells showed typical morphological features of apoptosis, as observed from normal inverted microscopy and Hoechst 33342 assay. Furthermore, girinimbine treatment resulted in DNA fragmentation and elevated levels of caspase-3 in HepG2 cells. Girinimbine treatment also displayed a time-dependent accumulation of the Sub-G(0)/G(1) …