Inhibitory effects of 17beta-estradiol and progesterone on ovarian carcinoma cell proliferation: a potential role for inducible nitric oxide synthase.
OBJECTIVE
Indirect evidence suggests that estrogen and progesterone are involved in the etiology of ovarian cancer (Oca). Estrogen and progesterone are also thought to modulate nitric oxide (NO) in human ovarian tumor tissue via regulation of inducible nitric oxide synthase (iNOS). Objectives in this study were: (1) to investigate the effects of 17beta-estradiol (E(2)) and progesterone (P(4)) on Oca cell proliferation employing elevated hormone concentrations occurring within the microenvironment of the ovary, and (2) to determine whether E(2) or P(4) affects iNOS expression and NO generation in Oca cells.


METHODS
Proliferation assays assessed the effects of E(2) and P(4) on cell growth in three human Oca cell lines (HOC-7, OVCAR-3, SKOV-3). Reverse transcriptase polymerase chain reaction was used to assess mRNA expression and Western blots to determine protein levels. NO generation was determined via the Griess reaction.


RESULTS
Elevated E(2), P(4), or E(2) plus P(4) (E + P), significantly inhibited HOC-7 cells and OVCAR-3 cells, but not SKOV-3 cells. E(2) at 10 microM downregulated iNOS expression and significantly reduced NO production in HOC-7 cells, while 10 microM P(4) or 10 microM E + P increased iNOS expression and NO production. Conclusions. Our findings demonstrate that elevated E(2), P(4), or E + P results in significant growth inhibition of Oca cells, and we propose a role for iNOS and NO in how these hormones modulate their activities in Oca cells.
Keith Bechtel
M
M
Department of Microbiology and Immunology, University of California at Los Angeles, Los Angeles, California, 90095, USA.
Bonavida
B
B
D015153:Blotting, Western; D002455:Cell Division / Q000187:drug effects; D017931:DNA Primers / Q000737:chemistry; D004958:Estradiol / Q000494:pharmacology*; D005260:Female; D006801:Humans; D009566:Nitrates / Q000378:metabolism; D019001:Nitric Oxide Synthase / Q000378:metabolism*; D052247:Nitric Oxide Synthase Type II; D009573:Nitrites / Q000378:metabolism; D010051:Ovarian Neoplasms / Q000188:drug therapy / Q000201:enzymology*; D011374:Progesterone / Q000494:pharmacology*; D011419:Propidium; D011956:Receptors, Cell Surface / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014407:Tumor Cells, Cultured / Q000187:drug effects* / Q000378:metabolism
D017931:DNA Primers; D009566:Nitrates; D009573:Nitrites; D011956:Receptors, Cell Surface; D011419:Propidium; D011374:Progesterone; D004958:Estradiol; C496319:NOS2 protein, human; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II