Growth inhibition and induction of apoptosis by 2-methoxyestradiol in rat osteosarcoma and malignant fibrous histiocytoma cell lines.
2-Methoxyestradiol (2-ME) has been found to possess antitumor activity in vivo and in vitro. It has been suggested that 2-ME induces apoptosis resulting in G2/M arrest of tumor cells. In this study, the effect of 2-ME was evaluated in rat osteosarcoma and malignant fibrous histiocytoma (MFH) cell lines. 2-ME was used at final concentrations of 100 nM to 2 microM. The effect of 2-ME on cell growth was measured by the MTS assay. Induction of apoptosis and activation of caspase-3 were investigated along with apoptosis-related gene expression. The data showed that 2-ME significantly inhibited cell growth, inducing apoptosis. The activity of caspase-3 was increased at 20 h and 40 h in both cell lines. 2-ME induced p16 expression, which was possibly involved in the apoptotic process. These results suggested that the 2-ME-induced apoptosis of rat osteosarcoma and rat MFH cells was accompanied by caspase-3 activation through p16 induction.
Fujii
Hiromasa
H
Department of Orthopedic Surgery, Nara Medical University, 840 Shijo-cho, Kashihara, Nara, Japan.
Honoki
Kanya
K
Tsujiuchi
Toshifumi
T
Kido
Akira
A
Yoshitani
Kazuhiro
K
Takakura
Yoshinori
Y
D000077584:2-Methoxyestradiol; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D053148:Caspase 3 / Q000235:genetics / Q000378:metabolism; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000235:genetics / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D004958:Estradiol / Q000031:analogs & derivatives* / Q000494:pharmacology; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D051677:Histiocytoma, Malignant Fibrous / Q000473:pathology*; D007202:Indicators and Reagents / Q000378:metabolism; D012516:Osteosarcoma / Q000473:pathology*; D012333:RNA, Messenger / Q000378:metabolism; D012334:RNA, Neoplasm / Q000032:analysis; D051381:Rats; D013778:Tetrazolium Salts / Q000378:metabolism; D050257:Tubulin Modulators / Q000494:pharmacology*
D000970:Antineoplastic Agents; D019941:Cyclin-Dependent Kinase Inhibitor p16; D007202:Indicators and Reagents; D012333:RNA, Messenger; D012334:RNA, Neoplasm; D013778:Tetrazolium Salts; D050257:Tubulin Modulators; D004958:Estradiol; D000077584:2-Methoxyestradiol; D053148:Caspase 3