Effects of mifepristone on proliferation of human gastric adenocarcinoma cell line SGC-7 901<i>in vitro</i>

Li, Da‐Qiang; Wang, Zhibiao; Bai, Jing; Zhao, Jie; Wang, Yuan; Hu, Kai; Du, Yiqi

doi:10.3748/wjg.v10.i18.2628

Cited by 28 publications

(29 citation statements)

References 19 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The remarkable inhibition of DNA synthesis induced by mifepristone was consistent with the abrupt interruption in cell growth observed within 24 h of exposure to the drug, the reduction in the number of cells in S phase, and the accumulation of cells in G 1 phase. Blockage of the cell cycle in G 1 after exposure to mifepristone has also been reported in human gastric adenocarcinoma cells (26), T-47D breast cancer cells (36), and in OVCAR-3 and A2780 ovarian cancer cells (27). In T-47D breast cancer cells, the inhibition of cell cycle progression by mifepristone was accompanied by induction of the cdk inhibitor p21 cip1 (36).…”

Section: Discussionmentioning

confidence: 99%

“…Furthermore, in a recent study using p53/BRCA1 -deficient mice, mifepristone prevented the formation of breast tumors (20), indicating its efficacy in not only impairing growth of established mammary tumors but also in inhibiting mammary tumorigenesis. Apart from breast cancer cells, mifepristone was reported to inhibit proliferation of normal and malignant endometrial cells (21 -24), prostate cancer cells (25), and gastric adenocarcinoma cell lines (26).…”

mentioning

confidence: 99%

See 1 more Smart Citation

Mifepristone Inhibits Ovarian Cancer Cell GrowthIn vitroandIn vivo

Goyeneche

Carón

Telleria

2007

Clinical Cancer Research

136

View full text Add to dashboard Cite

Purpose: These studies were designed to determine whether the synthetic steroid mifepristone inhibits ovarian cancer growth in vitro and in vivo and the molecular mechanisms involved. Experimental Design: The effect of mifepristone on ovarian cancer cell growth in vitro was studied in ovarian cancer cell lines of different genetic backgrounds (SK-OV-3, Caov-3, OV2008, and IGROV-1). In addition, the growth inhibition capacity of mifepristone on ovarian carcinoma xenografts was tested in nude mice. Results: Mifepristone inhibited ovarian cancer cell proliferation in a dose-and time-dependent manner. The cytostatic effect of mifepristone was confirmed in a clonogenic survival assay and was not linked to loss of viability. Mifepristone blocked DNA synthesis, arrested the cell cycle at the G 1 -S transition, up-regulated cyclin-dependent kinase (cdk) inhibitors p21 cip1 and p27 kip1 , down-regulated transcription factor E2F1, decreased expression of the E2F1-regulated genes cdk1 (cdc2) and cyclin A, and modestly decreased cdk2 and cyclin E levels. The abrupt arrest in cell growth induced by mifepristone correlated with reduced cdk2 activity, increased association of cdk2 with p21 cip1 and p27 kip1 , increased nuclear localization of the cdk inhibitors, and reduced nuclear abundance of cdk2 and cyclin E. In vivo, mifepristone significantly delayed the growth of ovarian carcinoma xenografts in a dose-dependent manner and without apparent toxic effects for the animals. Conclusions: These preclinical studies show that mifepristone is effective as a single agent in vitro and in vivo, inhibiting the growth of human epithelial ovarian cancer cells. Mifepristone markedly reduces cdk2 activity likely due to increased association of cdk2 with the cdk inhibitors p21 cip1 and p27 kip1 and reduced nuclear cdk2/cyclin E complex availability. Acting as a cytostatic agent, mifepristone promises to be of translational significance in ovarian cancer therapeutics.Mifepristone, commonly known as RU486, was first synthesized in the early 1980s and described as a progesterone receptor antagonist (1). The potent antagonism of mifepristone on uterine progesterone receptors led to its clinical application for termination of pregnancy, emergency contraception, luteal phase contraception, and menstrual regulation (2). However, when targeting cells other than uterine cells, the progesterone antagonistic activity of mifepristone is less clear. For instance, in fibroblasts and T47D breast cancer cells, treatment with activators of protein kinase A abrogated the antagonistic activity of mifepristone that instead elicited partial agonistic effects (3,4). In HeLa cells, mifepristone significantly induced progesterone-regulated reporter genes, and this agonistic effect was synergistically enhanced by elevating cyclic AMP or by overexpressing the catalytic subunit of protein kinase A (5). The molecular basis for the mixed agonist/antagonist transcriptional regulation of mifepristone in a cell type -specific manner seems to depend on the ratio...

show abstract

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

Mifepristone Inhibits Ovarian Cancer Cell GrowthIn vitroandIn vivo

Goyeneche

Carón

Telleria

2007

Clinical Cancer Research

136

View full text Add to dashboard Cite

show abstract

“…Several studies have demonstrated that mifepristone effectively inhibit the proliferation of certain types of hormone-dependent cancers such as progesterone receptor (PR)-positive breast cancer (14,15), ovarian cancer (16,17), endometrial cancer (18), prostate cancer (19), and gastric cancer (20). However, cervical carcinoma is a type of cancer that does not respond to hormonal treatment.…”

Section: Discussionmentioning

confidence: 99%

Cisplatin cytotoxicity is increased by mifepristone in cervical carcinoma: An in vitro and in vivo study

Jurado

Lopez-Flores²,

Álvarez³

et al. 2009

Oncol Rep

View full text Add to dashboard Cite

Abstract. We investigated the ability of mifepristone, an anti-progestin drug, to modulate the cytotoxic effect of cisplatin in two cervical cancer cell lines and in human xenograft cervical tumors. The effect of cisplatin alone or combined with mifepristone on cellular proliferation was studied with the XTT assay which use a tetrazolium dye {sodium3'-[1-(phenylamino-carbonyl)-3,4-tetrazolium],XTT}. Before and after treatment with mifepristone, the intracellular accumulation of cisplatin in cancer cells and tumors of mice was evaluated by HPLC. The expression of Bcl-2 and Bax genes was also assessed by a reverse transcriptase polymerase chain reaction (RT-PCR) and Western blotting. In addition, single agents and combination treatment in vivo studies were performed with the xenograft cervical model. Tumor measurements were carried out weekly. Analysis of the data by the isobologram method shows a synergistic antiproliferative effect produced by the combination of mifepristone with cisplatin only in the HeLa cervical cancer cell line but not in CaSki cells. The effect of mifepristone on cytotoxicity of cisplatin could be mediated, at least partially, by an increase of intracellular cisplatin accumulation, but not by changes in Bcl-2/Bax gene relation expression in these cells. In vivo studies showed that the combination of these agents has a significant antitumor activity against HeLa xenograft tumors. Our results suggest that mifepristone can improve the efficacy of the antiproliferative effect of cisplatin in vitro and in vivo. This anti-hormonal drug therapy may be a useful candidate for further evaluation in combination with other antineoplastic drugs in the treatment of cancer, particularly with cisplatin.

show abstract

“…It is interesting to note that the cells repopulating the culture after being exposed to 3 rounds of CDDP treatment in our model system grow at the same pace as cells never exposed to CDDP, indicating that the cells do not seem to be genetically damaged by previous CDDP treatment. MF has been known for displaying anti-growth properties in different human cell types (15)(16)(17)(19)(20)(21)(22). We recently began to elucidate the molecular mechanisms involved in this effect on ovarian cancer cell growth (23).…”

Section: Discussionmentioning

confidence: 99%

“…Yet, apart from this known contraceptive effect, MF has been reported to be effective as an anti-growth agent in endometriosis (15), leiomyomata (16), and breast (17,18), endometrial (19), prostate (20), gastric (21), and ovarian cancer cells (22). Our laboratory recently studied the molecular mechanisms of growth inhibition induced by MF in ovarian cancer cells and further defined its efficacy in an in vivo preclinical setting (23).…”

Section: Introductionmentioning

confidence: 99%

Mifepristone abrogates repopulation of ovarian cancer cells in between courses of cisplatin treatment

Freeburg

Goyeneche²,

Telleria

2009

Int J Oncol

View full text Add to dashboard Cite

Abstract. Repopulation of cancer cells escaping lethal chemotherapy is a critical factor hindering treatment success. One strategy to inhibit tumor cell repopulation is the use of cytostatic compounds between courses of lethal chemotherapy.In this study, we tested the hypothesis that mifepristone (MF), a steroid compound with demonstrated growth inhibition activity in ovarian cancer, should be efficacious in inducing cytostasis and preventing repopulation of ovarian cancer cells if given among rounds of cisplatin (CDDP) treatment. We established an in vitro approach wherein ovarian cancer cells with high (OV2008) or low (SK-OV-3) sensitivity to CDDP were exposed to 3 (OV2008) or 2 (SK-OV-3) rounds of lethal doses of CDDP for 1 h, 12 (OV2008) or 24 (SK-OV-3) days apart. Every 4 or 8 days cell number, cell viability, cell cycle traverse, and colony-forming capacity of viable cells was analyzed. Although CDDP killed the vast majority of cells, there were remnant cells escaping CDDP lethality and repopulating the culture, as evidenced by increased cell number, improved clonogenic capacity of viable cells, and normalization of DNA synthesis. Conversely, when cells were exposed to CDDP for 1 h, and 5, 10 or 20 μM MF was present in the culture medium after CDDP removal, the number, clonogenic capacity, and DNA synthesis ability of the cells were reduced in a dose-dependent manner. The blockage by MF of post-CDDP repopulation was accompanied by a remarkable increase in the percentage of cells expressing the cell death marker cleaved poly(ADP-ribose) polymerase and the mitotic marker phospho-histone H3, suggesting that MF also potentiated CDDP lethality and that the cells likely die due to mitotic failure. In summary, this is the first study reporting that presence of cytostatic concentrations of MF after courses of lethal doses of CDDP prevents repopulation of remnant ovarian cancer cells surviving CDDP treatment.

show abstract

Effects of mifepristone on proliferation of human gastric adenocarcinoma cell line SGC-7 901in vitro

Abstract: Mifepristone effectively inhibited the proliferation of PR-positive human gastric adenocarcinoma cell line SGC-7901 in vitro through multiple mechanisms, and may be a beneficial agent against human adenocarcinoma.

Cited by 28 publications

References 19 publications

Mifepristone Inhibits Ovarian Cancer Cell GrowthIn vitroandIn vivo

Mifepristone Inhibits Ovarian Cancer Cell GrowthIn vitroandIn vivo

Cisplatin cytotoxicity is increased by mifepristone in cervical carcinoma: An in vitro and in vivo study

Mifepristone abrogates repopulation of ovarian cancer cells in between courses of cisplatin treatment

Contact Info

Product

Resources

About