Antiandrogenic and apoptotic effects of RU-486 on animal prostate

Cabeza, Marisa; Bratoeff, Eugene; Heuze, Ivonne; Guzmán, Adrián; Gómez, Georgina; Berrios, Hilda; Rosales, Ana M.

doi:10.1016/j.jsbmb.2007.03.009

Cited by 7 publications

(7 citation statements)

References 18 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…In 2007 Cabeza et al [26] studied these interactions and found that the relative binding affinity of RU 486 for androgen receptors is 4.3%. Mifepristone significantly inhibited the prostate weights of hamsters at high doses in vivo and the immunohistochemistry analysis showed that, at 1 month postcastration, the hamster prostate was atropic.…”

Section: Prostate Cancermentioning

confidence: 99%

Selective progesterone receptor modulators 3: use in oncology, endocrinology and psychiatry

Benagiano

Bastianelli

Farris

2008

Expert Opinion on Pharmacotherapy

View full text Add to dashboard Cite

show abstract

Section: Prostate Cancermentioning

confidence: 99%

Selective progesterone receptor modulators 3: use in oncology, endocrinology and psychiatry

Benagiano

Bastianelli

Farris

2008

Expert Opinion on Pharmacotherapy

View full text Add to dashboard Cite

show abstract

“…Androgen bound to the AR translocates to the nucleus to modulate gene expression. The anti-progestin MIF has been known to inhibit the growth of prostate cancer cells [2,12,19]. MIF could induce apoptosis even in AR-negative DU-145 prostate cancer cells, which suggests that the cytotoxicity of MIF is not just based on androgen antagonistic activity.…”

Section: Discussionmentioning

confidence: 99%

“…MIF is a progesterone analogue and is known as a potent progesterone antagonist. MIF is also used as a selective androgen receptor (SAR) modulator because this compound interacts with AR and its corepressors [2,19]. Because of this strong AR antagonistic activity, MIF has been used in the treatment of prostate cancer.…”

Section: Introductionmentioning

confidence: 99%

“…Because of this strong AR antagonistic activity, MIF has been used in the treatment of prostate cancer. Although MIF has been known to inhibit prostate cancer cell growth in vitro and in vivo, its molecular mechanisms are not yet clear [2,6,20]. MIF can induce apoptosis in androgen-sensitive (LNCaP) and androgen-insensitive (PC-3, DU-145) cell lines [22].…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Effects of Mifepristone and Tamoxifen on Calcium Modulation in DU-145 Prostate Cancer Cells

Kim¹,

Kim²

2010

Journal of Life Science

View full text Add to dashboard Cite

Mifepristone (MIF) and Tamoxifen (TAM) have been used in the treatment of prostate cancer and breast cancer for more than a decade. MIF can induce apoptosis in both AR-positive and -negative prostate cancer cells. Because of its pleiotropic ligand-receptor properties, TAM exerts cytotoxic activity in estrogen (ER)-positive and various ER-negative cancer cells. However, the molecular mechanisms of these two substances are not yet clear. In the present work, we report that the cytotoxic effects of MIF and TAM are due to the modulation of intracellular Ca 2+ level in DU-145, androgen-insensitive cells. When the cells were treated with micromolar concentrations of either MIF or TAM, the growth and viability were significantly decreased in a dose-and time-dependent manner. The apoptosis induced by MIF or TAM was further proved and analyzed by confocal laser scanning microscopy (CLSM) and fluorescence-activated cell sorting (FACS). In the cells cultivated in a normal 1.5 mM Ca 2+ medium, both MIF and TAM also induced an increase of the intracellular Ca 2+ level in a dose-dependent fashion. Since a change in calcium level could not be found in cells of the Ca 2+ -free medium, the increase of intracellular Ca 2+ level might be due to an increase in extracellular calcium uptake. Our results show that the apoptotic effect was more prominent in TAM treatment compared to MIF treatment in DU-145 cells. The above findings might be due to the difference in the uppermost pathways of apoptosis induced by either MIF or TAM. When we checked the level of procaspase-8 activation, TAM showed minor level of activation, as opposed to MIF, which exerted strong activation. In both treatments, the levels of anti-apoptotic protein Bcl-2 decreased, and pro-apoptotic protein Bax level increased more than 2-fold. The activation of caspase-3, a key protease enzyme in the downstream pathway of apoptosis, was much higher in the cells treated with TAM, compared to the MIF treatment. The overall apoptotic activity shown in the present work was closely related to intracellular Ca 2+ concentration levels. Therefore, the cytotoxic activity induced by MIF and TAM might have been due to intracellular calcium modulation.

show abstract

“…Because of this strong AR antagonistic activity, MIF has been used in the treatment of prostate cancer. Although, MIF has been known to inhibit prostate cancer cell growth in vitro and in vivo, its molecular mechanisms are yet not clear [2,5,18,19]. MIF can induce apoptosis in androgen-sensitive (LNCaP) and androgen-insensitive (PC3, DU145) cell lines [21].…”

Section: Introductionmentioning

confidence: 99%

Cytotoxicity of Mifepristone via Calcium Modulation In Human Prostate Cancer Cells

2009

Journal of Life Science

View full text Add to dashboard Cite

MIF is a progesterone analogue and is known as a potent progesterone antagonist. Although MIF has been known to inhibit prostate cancer cell growth, its molecular mechanisms are not yet clear. In the present study, when the cells were treated for 2-4 days with 5-40 μM of MIF, the growth and viability of LNCaP cells were significantly decreased in a dose-and time-dependent manner. When the cells, cultivated in a normal 2 mM calcium concentration medium, were treated with 15 μM MIF for 1 day, the intracellular calcium level increased by 26% compared to the control. Similar results were also found in cells located in the calcium-free reaction buffer, indicating that MIF induced the increase of intracellular Ca 2+ levels, regardless of the presence of calcium in the surrounding medium. In the cells treated with various concentrations of MIF, the intracellular calcium levels increased in a dose dependent manner. Cells treated with MIF revealed typical early apoptotic signs, i.e., chromosome condensation and nuclei fragmentation. In cells treated with 40 μM MIF, Bcl-2 decreased to 19% of the control. The expression of Bax increased to almost 2 fold of the control. These results demonstrated very clearly that MIF treatment blocks the expression of Bcl-2 but stimulates the expression of Bax. According to the results of the present investigation, the apoptotic mechanism of MIF is triggered by intracellular modulation.

show abstract

Antiandrogenic and apoptotic effects of RU-486 on animal prostate

Cited by 7 publications

References 18 publications

Selective progesterone receptor modulators 3: use in oncology, endocrinology and psychiatry

Selective progesterone receptor modulators 3: use in oncology, endocrinology and psychiatry

Effects of Mifepristone and Tamoxifen on Calcium Modulation in DU-145 Prostate Cancer Cells

Cytotoxicity of Mifepristone via Calcium Modulation In Human Prostate Cancer Cells

Contact Info

Product

Resources

About