The aim of the study was to investigate the mechanism of action of somatostatin analogues (SSA), ionizing radiation, and their combination on pituitary adenoma cells with special emphasis on proliferative and apoptotic activity. In the 14 GH-secreting adenomas pretreated with SSA before surgery, more prominent regressive changes were found accompanied by compensatory increase in perivascular fibrosis than in the reference group of 17 unpretreated adenomas. The proliferative Ki-67 labeling index was significantly lower in the treated group (median 1.6 per 1000) than in the untreated patients (median 5.0 per 1000). Apoptosis was detected in only 2 of the 14 pretreated adenomas, and it was more frequent (9/17) and more prominent in the untreated group. In cell lines, the SSA had minimal antiproliferative effect, and they were unable to induce apoptosis. Ionizing radiation at doses of 5-20 Gy induced apoptosis in the corticotroph cell line AtT20 with no cell-cycle block. In the somatotroph GH3 cell line, the early (premitotic) apoptosis was detectable using only a high dose of 200 Gy; after irradiation with doses of 20-50 Gy, apoptosis appeared with the latency of 48-72 hours, and was preceded by cell-cycle arrest in the G(2)/M phase. The treatment with somatostatin-14 during irradiation increased the percentage of apoptotic cells in culture 10 days after irradiation (11% versus 3% using 20 Gy).

• MeSH
• Adenoma pathology   radiotherapy   surgery   MeSH
• Apoptosis physiology   radiation effects   MeSH
• Cell Division MeSH
• Cell Cycle radiation effects   MeSH
• Humans MeSH
• Biomarkers, Tumor analysis   MeSH
• Pituitary Neoplasms pathology   radiotherapy   surgery   MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Names of Substances
• Biomarkers, Tumor MeSH

Cultivation with 4-8 mumol/l hypericin (specific proteinkinase C inhibitor) activated by light induced high inhibition of the rate of HL-60 cell growth. When hypericin treated cells were not exposed to light growth inhibition was insignificant. Cultivation with light activated hypericin in concentration 16 mumol/l slightly inhibited growth rate of AtT20/D16v-F2 cells. AtT20/D16v-F2 cells did not proliferate in presence of light activated 32 mumol/l hypericin. Evidence of apoptosis was found in HL-60 cells treated with 1-8 mumol/l light activated hypericin, with maximum of apoptotic cells detected after 8 mumol/l light activated hypericin. Light activated hypericin induces both apoptosis and necrosis in dose and time dependent manners in HL-60 cells, but causes only necrosis in AtT20/D16v-F2 cells.

• MeSH
• Adenoma pathology   MeSH
• Anthracenes MeSH
• Apoptosis drug effects   MeSH
• Cell Division drug effects   MeSH
• Cell Cycle drug effects   MeSH
• DNA, Neoplasm analysis   drug effects   MeSH
• Photosensitizing Agents pharmacology   MeSH
• HL-60 Cells drug effects   pathology   MeSH
• Humans MeSH
• Mice MeSH
• Tumor Cells, Cultured drug effects   pathology   MeSH
• Pituitary Neoplasms pathology   MeSH
• Perylene analogs & derivatives   pharmacology   radiation effects   MeSH
• Protein Kinase C antagonists & inhibitors   MeSH
• Light * MeSH
• Dose-Response Relationship, Radiation MeSH
• Animals MeSH
• Check Tag
• Humans MeSH
• Mice MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Names of Substances
• Anthracenes MeSH
• DNA, Neoplasm MeSH
• Photosensitizing Agents MeSH
• hypericin MeSH Browser
• Perylene MeSH
• Protein Kinase C MeSH