Medroxyprogesterone acetate inhibits proliferation of colon cancer cell lines by modulating cell cycle-related protein expression.
OBJECTIVE
To investigate the effects of medroxyprogesterone acetate on colon cancer cells in vitro.


METHODS
HT29 and HCT116 human colon cancer cell lines were used in this study. Cell growth and WST-1 assays were performed to investigate the antiproliferative effect of medroxyprogesterone acetate. Cell cycle analysis was performed to investigate the effects of medroxyprogesterone acetate on cell cycle distribution. Western blot, immunoprecipitation, and a cyclin-dependent kinase assay were performed to investigate changes in the levels of cell cycle proteins.


RESULTS
Medroxyprogesterone acetate inhibited proliferation of the cancer cells by inducing accumulation in the G0/G1 fraction. Medroxyprogesterone acetate decreased expression of cyclin E, increased expression of p21(WAF1/CIP1), and enhanced interaction of p21(WAF1/CIP1) with cyclin-dependent kinase 2, eventually inhibiting its activity.


CONCLUSIONS
Medroxyprogesterone acetate exerts its antiproliferative effect by modulating cell cycle-related protein expression and cyclin-dependent kinase 2 activity. These results should help to elucidate the protective effect of medroxyprogesterone acetate on colon cancer risk.
Tanaka
Yoshihiro
Y
Department of Obstetrics and Gynecology, Graduate School of Medical Sciences, Kyushu University, Higashi-ku, Fukuoka, Japan.
Kato
Kiyoko
K
Mibu
Ryuichi
R
Uchida
Souko
S
Asanoma
Kazuo
K
Hashimoto
Kazunori
K
Nozaki
Masahiro
M
Wake
Norio
N
D002453:Cell Cycle / Q000187:drug effects / Q000502:physiology; D018797:Cell Cycle Proteins / Q000187:drug effects*; D045744:Cell Line, Tumor; D015179:Colorectal Neoplasms / Q000517:prevention & control*; D006801:Humans; D017258:Medroxyprogesterone Acetate / Q000494:pharmacology*; D011372:Progestins / Q000494:pharmacology*
D018797:Cell Cycle Proteins; D011372:Progestins; D017258:Medroxyprogesterone Acetate