Abstract Purpose: These studies were designed to determine whether the synthetic steroid mifepristone inhibits ovarian cancer growth in vitro and vivo molecular mechanisms involved. Experimental Design: The effect of on cell was studied lines different genetic backgrounds (SK-OV-3, Caov-3, OV2008, IGROV-1). In addition, inhibition capacity carcinoma xenografts tested nude mice. Results: Mifepristone inhibited proliferation a dose- time-dependent manner. cytostatic confirmed clonogenic...

Mifepristone (MF) has been largely used in reproductive medicine due to its capacity modulate the progesterone receptor (PR). The study of MF expanded field oncology; yet it remains unclear whether expression PR is required for act as an anti-cancer agent. Our laboratory shown that a potent inhibitor ovarian cancer cell growth. In this we questioned growth inhibitory properties observed cells would translate other cancers and non-reproductive origin and, importantly, efficacy related cognate...

Abstract Background Advanced ovarian cancer is treated with cytoreductive surgery and combination platinum- taxane-based chemotherapy. Although most patients have acute clinical response to this strategy, the disease ultimately recurs. In work we questioned whether synthetic steroid mifepristone, which as monotherapy inhibits growth of cells, capable preventing repopulation cells if given after a round lethal cisplatin-paclitaxel treatment. Methods We established an in vitro approach wherein...

Estradiol, together with PRL and placental lactogens, regulates steroidogenesis cell hypertrophy in the rat corpus luteum of pregnancy. Although binding experiments have demonstrated presence estrogen-binding sites, no evidence exists as to whether pregnancy expresses estrogen receptor (ER) genes. In this investigation, we analyzed expression two ER genes (ERα ERβ) (by RT-PCR situ hybridization) luteum, studied their developmental changes throughout pregnancy, investigated regulation ERα ERβ...

In this study, we investigated whether progesterone exerts an intraluteal action despite the lack of receptors (PR) in rat corpus luteum and acts through glucocorticoid receptor (GR) to enhance its own levels by down-regulating expression 20α-hydroxysteroid dehydrogenase (20α-HSD). We first established that constitutively expresses GR throughout pregnancy after parturition. also generated a temperature sensitive SV-40 transformed luteal cell line (GG-CL) 20α-HSD but lacks PR. Treatment with...

Abstract Background Changes in cell shape and plasticity cytoskeletal dynamics are critically involved adhesion, migration, invasion the overall process of metastasis. Previous work our laboratory demonstrated that synthetic steroid mifepristone inhibited growth highly metastatic cancer cells, while simultaneously causing striking changes cellular morphology. Here we assessed whether such morphological alterations developed response to cytostatic concentrations reversible or permanent,...

Mortalin (mot-2) induces inactivation of the tumor suppressor p53's transcriptional and apoptotic functions by cytoplasmic sequestration p53 in select cancers. The mot-2-dependent cytoprotective function enables cancer cells to support malignant transformation. Abrogating p53-mot-2 interaction can control or slow down growth cells. In this study, we report discovery a ubiquitin-like (UBX)-domain-containing protein, UBXN2A, which binds mot-2 consequently inhibits binding between p53. Genetic...

The corpora lutea of pregnancy in the rat are highly dependent on action PRL and PRL-like hormones to hypertrophy produce progesterone needed for maintenance gestation. Two forms receptor (PRL-R), designated as long (PRL-RL) short (PRL-RS), have been described tissues. To determine whether both present corpus luteum during examine developmental hormonal regulation their expression, total RNA isolated from at different stages luteinized granulosa cells subjected treatments were analyzed by...

Progesterone production by the corpus luteum (CL) is essential for preparation of endometrium implantation and maintenance gestation. modulates its own opposes functional luteal regression induced exogenous agents, such as prostaglandin F2α. In present study, we evaluated whether progesterone also capable interfering with process structural regression, which characterized a decrease in weight size gland because programmed cell death (i.e., apoptosis). We have found that low number cells...

This study was undertaken to investigate the regulation of mitochondrial manganese superoxide dismutase (Mn-SOD) and cytosolic copper-zinc SOD (Cu,Zn-SOD) in corpus luteum by inflammatory cytokines. We first examined developmental expression both mRNAs rat throughout pregnancy. mRNA levels were determined semiquantitative reverse transcription-polymerase chain reaction. Whereas Cu,Zn-SOD decreased during late pregnancy, Mn-SOD remained elevated. secondly effects reaction on luteal SODs. Rats...

The corpus luteum expresses two enzymes that scavenge superoxide radicals and protect the cells from their toxic activities: cytosolic copper, zinc-superoxide dismutase (Cu,Zn-SOD) mitochondrial manganese-SOD (Mn-SOD). present study was undertaken to investigate whether mRNA expression of each these is regulated by luteotropic hormones. Cu,Zn-SOD Mn-SOD levels were determined semi-quantitative reverse transcription-polymerase chain reaction (RT-PCR). We first examined effects prolactin (PRL)...

The synthetic steroid mifepristone blocks the growth of ovarian cancer cells, yet mechanism driving such effect is not entirely understood. Unbiased genomic and proteomic screenings using cell lines different genetic backgrounds sensitivities to platinum led identification two key genes upregulated by involved in unfolded protein response (UPR): master chaperone endoplasmic reticulum (ER), glucose regulated (GRP) 78 kDa, CCAAT/enhancer binding homologous transcription factor (CHOP). GRP78...

The corpus luteum is a transient endocrine gland specializing in the production of progesterone. regression involves an abrupt decline its capacity for producing progesterone followed by structural involution, which associated with apoptosis luteal cells. An vitro experimental approach needed to study molecular mechanisms underlying hormonal regulation cell death under defined conditions. In this study, we investigated simian virus-40-transformed cells determine whether they can be driven...

Antiprogestins have been largely utilized in reproductive medicine, yet their repositioning for oncologic use is rapidly emerging. In this study we investigated the molecular mediators of anti-ovarian cancer activity structurally related antiprogestins RU-38486, ORG-31710 and CDB-2914. We studied responses wt p53 OV2008 null SK-OV-3 cells to varying doses The steroids inhibited growth both cell lines with a potency RU-38486 > CDB-2914, were cytostatic at lower but lethal higher...

Changes in progesterone production were analysed after intrabursal ovarian administration of the antiprogesterone RU486, mifepristone, rats at pro-oestrus and during pregnancy.RU486 was administered 09:00\p=n-\10:00h serum measured 8 h treatment, except for those on days 3 12 pregnancy when steroid 4, 24 later.RU486 stimulates day 3\p=n-\5 15\p=n-\20 pregnancy.Conversely, treatment with antiprogestagen inhibits 7\p=n-\14of gestation.The inhibition (day 12) or stimulation 19) induced by RU486...

Repopulation of cancer cells escaping lethal chemotherapy is a critical factor hindering treatment success. One strategy to inhibit tumor cell repopulation the use cytostatic compounds between courses chemotherapy. In this study, we tested hypothesis that mifepristone (MF), steroid compound with demonstrated growth inhibition activity in ovarian cancer, should be efficacious inducing cytostasis and preventing if given among rounds cisplatin (CDDP) treatment. We established an vitro approach...

Interleukin (IL)-6, a multifunctional cytokine originally described as T cell-derived factor, is also produced by different cell types, and it influences wide variety of physiological pathophysiological processes. Recent studies further suggest that IL-6 has role in down-regulating hormone production endocrine organs can negatively affect the steroidogenic capacity both ovaries testes. Thus, aims this investigation were to examine whether plays luteolysis and, more specifically, determine...

PRL has been shown to stimulate mRNA expression of both ERα and ERβ in the rat corpus luteum decidua pregnancy. To investigate whether may ER at level transcription which factors mediate this stimulation, we have cloned 5′-flanking regions genes. A constitutively active receptor (PRL-RCA) stimulated promoter activity, indicating that is acting transcription. Putative signal transducer activator (Stat)5 response elements were identified −189 −330 promoter. Mutation these or overexpression...