nitrophenols and Carcinoma

ABT‑737 is a recently reported inhibitor of members of the Bcl‑2 family of apoptosis regulators. However, to the best of our knowledge, its necroptosis‑inducing function in bladder cancer has not yet been researched. Thus, the present study aimed to investigate whether this Bcl‑2 family inhibitor can induce both apoptosis and necroptosis of urothelial carcinoma cells. The proliferation and survival of urothelial carcinoma cell lines treated with a combination of both Z‑VAD‑FMK as a pan‑caspase inhibitor and ABT‑737 were assessed in vitro. Z‑DNA binding protein 1 (ZBP1), receptor‑interacting protein (RIP)1 and RIP3 were knocked down using small interfering RNA in urothelial carcinoma cell lines. The protein expression levels of ZBP1, RIP1 and RIP3 following cell transfection were measured via western blot analysis. Cell viability was determined using an MTT assay. Cell invasion was examined using cell invasion assays. The expression levels of necroptosis‑related proteins, high mobility group box 1, ZBP1, mixed‑lineage kinase domain‑like protein (MLKL) and RIP3, were measured via western blotting. It was found that ABT‑737 inhibited the proliferation and invasion of bladder cancer cells by inducing cell necrosis. The data demonstrated that ZBP1 and RIP3 have main roles in the cell necrosis induced by ABT‑737. In addition, RIP3 and ZBP1, without interacting with RIP1, directly induced MLKL‑mediated programmed cell necrosis. Thus, understanding how urothelial carcinoma cells react to Bcl‑2 family inhibitors may accelerate the discovery of drugs to treat bladder cancer.

Topics: Antineoplastic Agents; Apoptosis; Biphenyl Compounds; Carcinoma; Cell Line, Tumor; Humans; Necroptosis; Nitrophenols; Nuclear Pore Complex Proteins; Piperazines; Protein Kinases; Proto-Oncogene Proteins c-bcl-2; Receptor-Interacting Protein Serine-Threonine Kinases; RNA-Binding Proteins; Sulfonamides; Urinary Bladder Neoplasms

To investigate the metabolic enzymatic capacity of the colon mucosa to detoxify noxious carcinogenic compounds.. We investigated the activity of 2 conjugating enzymes-the microsomal uridine glucuronosyltransferase (UGT) and the cytosomal glutathione S-transferase (GST) in the uninvolved mucosa of the colon transversum and sigmoideum in patients with adenomatous polyps and colorectal cancer. Biopsies were taken from the mucosa during colonoscopies which were done for clinical (diagnostic) reasons. After storage, the biopsy material was homogenized and after differential centrifugation the enzyme assays were performed with 4-nitrophenol (UGT) and 1-chloro 2,4-dinitrobenzene (GST) as substrates.. About 48 patients were included of which 28 had adenomas and 20 had colorectal carcinomas confirmed by histopathology. Enzyme activities were expressed as nmol/mg per minute protein for the GST and as pmol/mg per minute protein for the UGT. Analysis of variance (F-test) indicated that both enzymes were more widely distributed in adenoma than in cancer patients. The means ± SD were smaller for cancer patients: GST for adenomas 268 ± 152 vs 241 ± 69 for carcinomas and UGT for adenomas 197 ± 200 vs 150 ± 86 for carcinomas.. Compared to patients with adenomatous colon polyps those with colorectal carcinoma exhibited a lower capacity of detoxifying enzyme metabolism and their activities clustered over a smaller range.

Topics: Adenoma; Adult; Aged; Aged, 80 and over; Biomarkers, Tumor; Biopsy; Carcinoma; Colonic Neoplasms; Dinitrochlorobenzene; Disease Progression; Female; Glucuronosyltransferase; Glutathione Transferase; Humans; Inactivation, Metabolic; Linear Models; Male; Middle Aged; Nitrophenols; Substrate Specificity

This study investigated the potential synergistic effects of two inducers of apoptosis: the small molecule ABT-737 and arsenic trioxide (ATO).. Human gastric carcinoma cell lines SGC-7901 and MGC-803 were used to determine the effects of ABT-737 and ATO (alone or in combination) on cell proliferation and apoptosis in vitro. In vivo effects of these drugs were investigated in SGC-7901 solid tumours, grown in immunodeficient mice.. ABT-737 and ATO inhibited proliferation and induced apoptosis in SGC-7901 and MGC-803 cells in concentration- and time-dependent manners, and showed a synergistic effect. ABT-737 disturbed the binding of B cell lymphoma (Bcl)-2 homologous antagonist killer and Bcl-extra large; ATO downregulated myeloid cell leukaemia (Mcl)-1 protein and upregulated Mcl-1short, the short splicing variant. ABT-737 and ATO significantly suppressed SGC-7901 xenograft growth, synergistically inhibited tumour growth and induced apoptosis in vivo.. This study provides preclinical evidence that ABT-737 and ATO synergize to induce apoptosis of gastric carcinoma cells, suggesting that further investigation of these agents (as potential treatments for gastric cancer) is warranted.

Topics: Animals; Antineoplastic Combined Chemotherapy Protocols; Apoptosis; Apoptosis Regulatory Proteins; Arsenic Trioxide; Arsenicals; Biphenyl Compounds; Carcinoma; Cell Line, Tumor; Cell Proliferation; Drug Synergism; Humans; Male; Mice; Mice, Inbred BALB C; Mice, Nude; Nitrophenols; Oxides; Piperazines; Stomach Neoplasms; Sulfonamides; Tumor Burden; Xenograft Model Antitumor Assays

Interaction of microgram quantities of highly purified rabbit anti-TNP antibodies with TNP-substituted HeLa, HEp-2, and L cells caused an intense stimulation of radioactive nucleoside ([(125)I]UdR and [(3)H]TdR) uptake which was maximal 24-72 h after exposure of cells to antibody. The stimulation of nucleoside uptake and presumaly DNA synthesis was shown to be immuno logically mediated because unsubstituted cells were not stimulated by anti-TNP antibody, normal rabbit gamma globulin did not stimulate TNP-cells, and a hapten inhibitor, epsilon-DNP-lysine, prevented the stimulation of TNP-cells by anti-TNP antibody. These findings demonstrate that interaction of antibody with cell surface antigen can alter cell membrane transport, and possibly can enhance cell growth.

Topics: Animals; Antibodies; Carcinoma; Cell Line; Female; Glucose Oxidase; HeLa Cells; Humans; Idoxuridine; Iodides; Iodine Radioisotopes; Kinetics; L Cells; Laryngeal Neoplasms; Mice; Neoplasms; Nitrophenols; Peroxidases; Thymidine; Tritium; Trypsin

Tumor cell lines exposed to immunoglobulins specific for cell surface antigens developed increased cellular incorporation of [(125)I]iododeoxyuridine and [(3)H]thymidine (up to 200-fold increases over cells treated with normal rabbit immunoglobulins). Antibody-stimulated cells multiplied more rapidly and lived longer than control cells in tissue culture. These observations were made both with cells substituted with 2,4,6-trinitrophenol and purified antibody against 2,4,6-trinitrophenol, and with several cell lines and their respective whole-cell antibodies. Antibodies that were stimulatory at low concentrations were cytotoxic at high concentrations. These observations may have significance in regard to enhancing effects of antibodies on tumor cell growth in vivo.

Topics: Animals; Antibodies, Neoplasm; Carcinoma; Cell Line; Colonic Neoplasms; Cross Reactions; DNA, Neoplasm; Epitopes; Female; HeLa Cells; Humans; Idoxuridine; Iodine Radioisotopes; Laryngeal Neoplasms; Mice; Neoplasms; Nitrophenols; Plasmacytoma; Rabbits; Thymidine; Tritium

Topics: Acid Phosphatase; Blood Cell Count; Blood Coagulation Tests; Blood Platelets; Carcinoma; Clot Retraction; Depression, Chemical; Heparin; Humans; Male; Nitrophenols; Prostatic Neoplasms; Temperature; Thrombocytopenia

Topics: Animals; Carcinoma; Carcinoma, Ehrlich Tumor; Dicumarol; Glucosamine; Glucose; Metabolism; Nitrophenols; Phenazines