title: [2-methoxyestradiol induces p53 independent apoptosis in pancratic carcinoma and inhibits growth of lung metastasis].
abstract: 2-methoxyestradiol (2-ME) is able to inhibit growth of certain tumors. We were interested in studying this effect of 2-ME on pancreatic cancer. In three out of four cell lines, 2-ME induced 50-90% growth inhibition after 48 hours treatment with 2 microM 2-ME. TUNEL staining for apoptosis revealed that after treatment with 2 microM 2-ME for 48 hours 37-97% of these cells underwent apoptotic cell death (p < 0.005-0.0001). Since all cell lines used harbor a p53 mutation, this apoptosis appears to be p53 independent. One of these cell lines (MIAPaCa-2) was used for the in vivo experiment in nude mice. After a daily oral administration of 1 mg 2-ME for three weeks, the number of lung metastases could be reduced by 59%, as compared to the control non treated group (p < 0.0005). No signs of toxicity were seen. It appears that 2-ME is a potent compound for the treatment of pancreatic cancer, which might be interesting for clinical application.
mesh_terms: D000077584:2-Methoxyestradiol; D000818:Animals; D018931:Antineoplastic Agents, Hormonal / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects* / Q000235:genetics; D002455:Cell Division / Q000187:drug effects* / Q000235:genetics; D004958:Estradiol / Q000031:analogs & derivatives / Q000494:pharmacology*; D006801:Humans; D020287:In Situ Nick-End Labeling; D008168:Lung / Q000473:pathology; D008175:Lung Neoplasms / Q000235:genetics / Q000473:pathology / Q000556:secondary*; D051379:Mice; D008819:Mice, Nude; D009154:Mutation / Q000235:genetics; D009368:Neoplasm Transplantation / Q000473:pathology; D010190:Pancreatic Neoplasms / Q000235:genetics / Q000473:pathology*; D014407:Tumor Cells, Cultured / Q000187:drug effects* / Q000473:pathology / Q000637:transplantation; D016159:Tumor Suppressor Protein p53 / Q000235:genetics*
chemical_list: D018931:Antineoplastic Agents, Hormonal; D016159:Tumor Suppressor Protein p53; D004958:Estradiol; D000077584:2-Methoxyestradiol