title: Effect of combined treatment with progesterone and tamoxifen on the             growth and apoptosis of human ovarian cancer cells.
abstract: Progesterone has a potential protective effect against ovarian carcinoma             induced by estrogen. Progesterone is also known to cause apoptosis while tamoxifen             induces growth arrest. Therefore, we attempted to determine whether combined treatment             with progesterone and tamoxifen has a synergistic effect on anti-cancer activity.             Although progesterone is known to cause apoptosis while tamoxifen induces growth             arrest in many cancer cells, the detailed action of progesterone and tamoxifen             and the anticancer effect of combined treatment have not been tested in ovarian             cancer cells. Therefore, we tested the growth and apoptosis activity of progesterone             and tamoxifen and the anticancer effect of combined treatment of progesterone             and tamoxifen in ovarian cancer cells. Ovarian cancer cells, PA-1, were treated             with progesterone, tamoxifen, or a combination of progesterone and tamoxifen.             The anti-cancer effects were investigated by use of flow cytometry, terminal deoxynucleotidyl             transferase dUTP nick end labeling (TUNEL) assay, DNA fragmentation analysis,             and Western blot analysis. We found that 100 µM progesterone induced typical apoptosis             in PA-1 cells. Treatment of PA-1 cells with 10 µM tamoxifen resulted in an increase             in the levels of p21, p27, p16 and phospho-pRb, indicating typical G1 arrest.             Co-treatment of PA-1 cells with 100 µM progesterone and 10 µM tamoxifen resulted             in typical apoptosis, similar to that induced by treatment with 100 µM progesterone             alone. These results indicate that progesterone caused apoptosis and tamoxifen             induced G1 arrest. Combined treatment with tamoxifen and progesterone caused apoptosis             similar to that induced by treatment with progesterone alone and had no additional             anti-cancer effect in ovarian cancer cells.
authors.affiliation: Department of Obstetrics and Gynecology, Sisters of Charity Hospital,                     State University of New York at Buffalo, Buffalo, NY 14214, USA.
authors.forename: Ji-Young
authors.initials: JY
authors.lastname: Lee
authors.forename: Jong-Yeon
authors.initials: JY
authors.lastname: Shin
authors.forename: Hyun-Seok
authors.initials: HS
authors.lastname: Kim
authors.forename: Jee-In
authors.initials: JI
authors.lastname: Heo
authors.forename: Yoon-Jung
authors.initials: YJ
authors.lastname: Kho
authors.forename: Hong-Jun
authors.initials: HJ
authors.lastname: Kang
authors.forename: Seong-Hoon
authors.initials: SH
authors.lastname: Park
authors.forename: Jae-Yong
authors.initials: JY
authors.lastname: Lee
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D015153:Blotting, Western; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects; D053938:DNA Fragmentation / Q000187:drug effects; D004357:Drug Synergism; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D020287:In Situ Nick-End Labeling; D010051:Ovarian Neoplasms / Q000473:pathology*; D011374:Progesterone / Q000494:pharmacology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013629:Tamoxifen / Q000494:pharmacology*
chemical_list: D000970:Antineoplastic Agents; D013629:Tamoxifen; D011374:Progesterone