naphthoquinones and Carcinoid-Tumor

The aim of this study was to investigate the apoptosis resulting from NSC 95397, brefeldin A, bortezomib and sanguinarine in neuroendocrine tumor cell lines.. A multiparametric high-content screening assay for measurement of apoptosis was used. The human pancreatic carcinoid cell line, BON-1, human typical bronchial carcinoid cell line NCI-H727 and the human atypical bronchial carcinoid cell line NCI-H720 were tested. After incubation with cytotoxic drugs, the DNA-binding dye Hoechst 33342, fluorescein-tagged probes that covalently bind active caspase-3 and chloromethyl-X-rosamine to detect mitochondrial membrane potential were added. Image acquisition and quantitative measurement of fluorescence was performed using automated image capture and analysis instrument ArrayScan. In addition, nuclear morphology was examined on microscopic slides stained with May-Grunewald-Giemsa.. A time- and dose-dependent activation of caspase-3 and increase in nuclear fragmentation and condensation were observed for the drugs using a multiparametric apoptosis assay. These results were confirmed with nuclear morphological examination on microscopic slides.. NSC 95397, brefeldin A, bortezomib and sanguinarine induced caspase-3 activation with modest changes in nuclear morphology.

Topics: Apoptosis; Benzophenanthridines; Boronic Acids; Bortezomib; Brefeldin A; Carcinoid Tumor; Carcinoma, Bronchogenic; Cell Line, Tumor; Drug Screening Assays, Antitumor; Humans; Isoquinolines; Lung Neoplasms; Naphthoquinones; Neuroendocrine Tumors; Pancreatic Neoplasms; Pyrazines

There is a large need for better pharmacological treatment of neuroendocrine tumors. The aim of this study was to investigate and quantify the cytotoxic potentiating effects resulting from a combination of five substances, NSC 95397, emetine, CGP-74514A hydrochloride, Brefeldin A and sanguinarine chloride, chosen from a previous screening of 1,280 pharmacologically active agents on neuroendocrine tumor cells, with standard cytotoxic agents currently used in the treatment of neuroendocrine tumors.. The human pancreatic carcinoid cell line BON-1, human typical bronchial carcinoid cell line NCI-H727 and the human atypical bronchial carcinoid cell line NCI-H720 were used. Combinations between doxorubicin, etoposide, oxaliplatin, docetaxel, and each one of the five agents were studied and simultaneous exposures were explored using the median-effect method.. Most of the combinations of NSC-95397 and emetine with doxorubicin, etoposide, docetaxel, and oxaliplatin showed synergism, and their remaining combinations were additive. Almost all of the CGP-74514A hydrochloride interactions were additive, while brefeldin A and sanguinarine displayed less synergy but more additive and antagonistic interactions in combination with the standard drugs.. The synergistic and additive interactions make NSC-95397, emetine, and CGP-74514A hydrochloride potential candidates for incorporation into combination chemotherapy regimens and these drugs might be the suitable candidates for further clinical studies in patients with bronchial carcinoids and pancreatic endocrine tumors.

Topics: 2-Aminopurine; Antineoplastic Combined Chemotherapy Protocols; Bronchial Neoplasms; Carcinoid Tumor; Cell Line, Tumor; Drug Screening Assays, Antitumor; Drug Synergism; Emetine; Humans; Naphthoquinones; Neuroendocrine Tumors; Pancreatic Neoplasms