Estrogen and progesterone lower cyclin B1 AND D1 expression, block cell cycle in G2/M, and trigger apoptosis in human adrenal carcinoma cell cultures.
The effects of 17 beta-estradiol and progesterone were evaluated separately and in combination, on the growth, survival, and cell cycle dynamics of SW-13 human adrenal carcinoma cells in culture. Both hormones significantly decreased cell survival, with dose response curves at four days demonstrating EC (50)s estimated at 1.2 x 10 (-5) M for 17 beta-estradiol and 4.8 x 10 (-6) M for progesterone. Flow cytometry studies of these cultures indicated a strong G2/M blocking effect of both steroids, either individually or in combination; the effects of progesterone and of both agents together were substantially greater than the effect with 17 beta-estradiol alone. The sub-G1 region of the flow cytometry profile was significantly enhanced by exposure to 17 beta-estradiol and even more by progesterone. Sub-G1 "apoptosis" was confirmed by fragmented and condensed nuclear chromatin staining using a standard DAPI fluorescence assay. The expression of the critical cell cycle regulatory proteins cyclin B1 and D1 were significantly decreased by each hormone, with the influence of progesterone again predominating. These data demonstrate that high doses of 17 beta-estradiol and progesterone have inhibitory and apoptotic effects on SW-13 human adrenal carcinoma cells IN VITRO. The observed effects are associated with declines in cyclin B1 and D1 expression as well as a block in G2/M.
Brown
J W
JW
Adrenal Research Laboratory, V. A. Medical Center, Miami, FL, USA. j.brown@miami.edu
Prieto
L M
LM
Perez-Stable
C
C
Montoya
M
M
Cappell
S
S
Fishman
L M
LM
D000310:Adrenal Gland Neoplasms / Q000378:metabolism* / Q000473:pathology; D017209:Apoptosis / Q000187:drug effects*; D002455:Cell Division / Q000187:drug effects*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D019926:Cyclin B / Q000096:biosynthesis*; D056744:Cyclin B1; D056741:Cyclin D; D016213:Cyclins / Q000096:biosynthesis*; D004305:Dose-Response Relationship, Drug; D004958:Estradiol / Q000494:pharmacology*; D004967:Estrogens / Q000494:pharmacology*; D016195:G2 Phase / Q000187:drug effects*; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D006801:Humans; D009363:Neoplasm Proteins / Q000096:biosynthesis*; D011374:Progesterone / Q000494:pharmacology*; D011372:Progestins / Q000494:pharmacology*
C534699:CCNB1 protein, human; D019926:Cyclin B; D056744:Cyclin B1; D056741:Cyclin D; D016213:Cyclins; D004967:Estrogens; D009363:Neoplasm Proteins; D011372:Progestins; D011374:Progesterone; D004958:Estradiol