Potent antitumor activity of 2-methoxyestradiol in human pancreatic cancer cell lines.
We examined the effect of 2-methoxyestradiol (2-ME) on the growth and tumorigenesis of human pancreatic cancer cells. 2-ME inhibited the growth of these cell lines (50-90%) in a dose- and time-dependent fashion, and terminal deoxynucleotidyl transferase staining showed that it induced apoptotic cell death. Flow cytometric analysis indicated that 2-ME-sensitive cells showed a prolonged S phase after 48 h of treatment. We used a mouse model for in vivo studies of lung metastasis and injected MIA PaCa-2 cells into the tail veins of nu/nu mice; lung colonies were formed. Mice given oral 2-ME showed 60% inhibition in the number of lung colonies compared with control, untreated animals. These results suggest that 2-ME may have clinical application for the treatment of pancreatic cancer.
Schumacher
G
G
Department of General Surgery and Transplantation, Charite Campus Virchow Klinikum, Berlin, Germany.
Kataoka
M
M
Roth
J A
JA
Mukhopadhyay
T
T
D000077584:2-Methoxyestradiol; D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D017209:Apoptosis; D002455:Cell Division / Q000187:drug effects; D053938:DNA Fragmentation / Q000187:drug effects; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004958:Estradiol / Q000031:analogs & derivatives* / Q000627:therapeutic use; D006801:Humans; D008175:Lung Neoplasms / Q000473:pathology / Q000517:prevention & control / Q000556:secondary; D051379:Mice; D008819:Mice, Nude; D009362:Neoplasm Metastasis; D009368:Neoplasm Transplantation; D010190:Pancreatic Neoplasms / Q000188:drug therapy* / Q000473:pathology; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; D004958:Estradiol; D000077584:2-Methoxyestradiol