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J R Pasqualini - One of the best experts on this subject based on the ideXlab platform.
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Human estrogen sulfotransferase (hEST1) activities and its mRNA in various breast cancer cell lines. Effect of the progestin, Promegestone (R-5020).
The Journal of steroid biochemistry and molecular biology, 1998Co-Authors: G Chetrite, E Le Nestour, J R PasqualiniAbstract:Using reverse transcriptase-polymerase chain reaction amplification it was possible to detect the presence of type 1 human estrogen sulfotransferase (hEST1) mRNA in the hormone-dependent: MCF-7 and T-47D, and hormone-independent: MDA-MB-231 and MDA-MB-468, human breast cancer cells. The expression of this mRNA is significantly higher in the MDA-MB-468 cells and a correlation of this mRNA expression with the enzymatic activity was observed. The progestin Promegestone (R-5020) at a low concentration (5 x 10(-7) M) can significantly increase the estrogen sulfotransferase activity and its mRNA in the hormone-dependent MCF-7 and T-47D cells. As estrogen sulfates are biologically inactive, the stimulatory effect on sulfotransferase by Promegestone may open attractive possibilities in the control of estradiol in human breast cancer.
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estrone sulfate sulfatase and 17β hydroxysteroid dehydrogenase activities a hypothesis for their role in the evolution of human breast cancer from hormone dependence to hormone independence
The Journal of Steroid Biochemistry and Molecular Biology, 1995Co-Authors: J R Pasqualini, Bachlien Nguyen, C Maloche, L Delalonde, Marwa Talbi, M C Feinstein, Joaquin Botella, Catherine Blacker, Gérard Chetrite, J. ParisAbstract:Abstract The evaluation of estrogens (estrone, estradiol, and their sulfates) in the breast tissue of post-menopausal patients with breast cancer indicates high levels, particularly of estrone sulfate (E 1 S) which is 15–25 times higher than in the plasma. Breast cancer tissue contains the enzymes necessary for local synthesis of estradiol and it was demonstrated that, despite the presence of the sulfatase and its messenger in hormone-dependent and hormone-independent breast cancer cells, this enzyme operates particularly in hormone-dependent cells. Different progestins: Nomegestrol acetate, Promegestone, progesterone, as well as Danazol, can block the conversion of E 1 S to E 2 very strongly in hormone-dependent breast cancer cells. The last step in the formation of estradiol is the conversion of E 1 to this estrogen by the action of 17β-hydroxysteroid dehydrogenase. This activity is preferentially in the reductive direction (formation of E 2 ) in hormone-dependent cells, but oxidative (E 2 → E 1 ) in hormone-independent cells. Using intact hormone-dependent cells it was observed that Nomegestrol acetate can block the conversion of E 1 to E 2 . It is concluded, firstly, that in addition to ER mutants other factors are involved in the transformation of hormone-dependent breast cancer to hormone-independent, this concerns the enzymatic activity in the formation of E 2 ; it is suggested that stimulatory or repressive factor(s) involved in the enzyme activity are implicated as the cancer evolves to hormone-independence; secondly, different drugs can block the conversion of E 1 S to E 2 . Clinical trials of these “anti-enzyme” substances in breast cancer patients could be the next step to investigate new therapeutic possibilities for this disease.
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transformation of estrone and estradiol in hormone dependent and hormone independent human breast cancer cells effects of the antiestrogen ici 164 384 danazol and Promegestone r 5020
Breast Cancer Research and Treatment, 1995Co-Authors: Bachlien Nguyen, G Chetrite, J R PasqualiniAbstract:Using different hormone-dependent (MCF-7, T-47D) and hormone-independent (MDA-MB-231, Hs-578S, MDA-MB-436) human breast cancer cells, the interconversion estrone (E1) ⇌ estradiol (E2) was explored. The data show very clearly that in the hormone-dependent cells the tendency is to form E2 after incubation with E1, whereas after incubation with E2 most of this estrogen remains unchanged. In the hormone-independent cells, in contrast most of E1 remains E1, while E2 is converted into E1. The tendency of the reductive ⇌ oxidative direction is supported by the analysis of estrogens in the culture medium. To explore the possible action of different drugs on the 17β-hydroxysteroid dehydrogenase (17β-HSD) activity, it was observed that the potent antiestrogen ICI 164,384 inhibits the conversion of E1 to E2, while a lesser effect is observed with Danazol and only weak inhibition is obtained with the progestagen Promegestone (R-5020). It is concluded that the orientation of 17β-HSD activity for the interconversion E1 ⇌ E2 in hormone-dependent and -independent cells is related to the hormonal status of the cells.
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effect of the progestagen Promegestone r 5020 on mrna of the oestrone sulphatase in the mcf 7 human mammary cancer cells
Anticancer Research, 1994Co-Authors: J R Pasqualini, C Maloche, M Maroni, G ChetriteAbstract:: Using reverse transcriptase polymerase chain reaction amplification it was possible to detect the presence of oestrogen sulphatase mRNA in different hormone-dependent (MCF-7, T-47D) and hormone-independent (MDA-MB-231, MDA-MB-468) mammary cancer cell lines. The expression of this mRNA is significantly higher in T-47D and MDA-MB-231 than in the other cell lines, and a correlation of this expression with the enzymatic activities was observed. The progestagen Promegestone (R-5020) can significantly decrease the mRNA of the sulphatase in MCF-7 cells. As this progestagen can also inhibit the enzyme itself in the same mammary cancer cell line, it is suggested that for the decrease in the sulphatase activity not only the effect on the enzyme, but also the effect on transcriptional factor(s) which express this enzyme are involved. The present data not only contribute to the knowledge of the mechanism of the sulphatase activity, but also can open new possibilities in breast cancer treatment.
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effect of Promegestone tamoxifen 4 hydroxytamoxifen and ici 164 384 on the oestrone sulphatase activity of human breast cancer cells
Anticancer Research, 1993Co-Authors: G Chetrite, L Delalonde, C Varin, J R PasqualiniAbstract:In the present study, we explored the effects on sulphatase activity by Promegestone (R-5020), Tamoxifen (TAM), 4-hydroxytamoxifen (4-OH-TAM) and ICI 164,384 in the T-47D hormone-dependent and MDA-MB-231 hormone-independent mammary cancer cell lines. Using homogenates of these cells it was observed that Promegestone has a significant effect on the inhibition of oestrone (E1) sulphatase activity. As this effect is competitive, it is suggested that there is a direct action of this compound on the enzyme. Tamoxifen has very little or no effect, 4-hydroxytamoxifen has an intermediate effect and ICI 164,384 is active in the enzyme inhibition, particularly with MDA-MB-231 cells. The present data could open new possibilities for human breast cancer treatment, as sulphatase is very active in the first step of the conversion of oestrone sulphate (E1S) to oestradiol (E2), and oestradiol is one of the principal carcinogenic factors in human hormone-dependent breast cancer.
G Chetrite - One of the best experts on this subject based on the ideXlab platform.
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correlation of estrogen sulfotransferase activity and proliferation in normal and carcinomatous human breast a hypothesis
Anticancer Research, 2007Co-Authors: Jorge R. Pasqualini, G ChetriteAbstract:. Background: Sulfotransferases are present in normal and cancerous human breast tissues. The purpose of this article is to present a hypothetical correlation of sulfotransferase activity with proliferation in breast cancer. Materials and Methods: Sulfotransferases were evaluated in breast cancer cells by determining the transformation of nonconjugated estrogens to the sulfates. Proliferation was evaluated by the action on cell growth or the size of a transplanted tumor. The effect was obtained using the progestins: nomegestrol acetate, Promegestone, and medrogestone, as well as tibolone and its metabolites at concentrations of 5x10 -5 to 5x10 -9 M. Results: A possible correlation of sulfotransferase activity stimulation and cell growth inhibition provoked by the various progestins used, or by tibolone and its metabolites was shown. Conclusion: It is suggested that the antiproliferative effect of these compounds could be related to the decrease of bioactive estradiol by the formation of its biologically inactive sulfate as a consequence of the stimulatory effect by the various progestins or tibolone on sulfotransferase activity.
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Human estrogen sulfotransferase (hEST1) activities and its mRNA in various breast cancer cell lines. Effect of the progestin, Promegestone (R-5020).
The Journal of steroid biochemistry and molecular biology, 1998Co-Authors: G Chetrite, E Le Nestour, J R PasqualiniAbstract:Using reverse transcriptase-polymerase chain reaction amplification it was possible to detect the presence of type 1 human estrogen sulfotransferase (hEST1) mRNA in the hormone-dependent: MCF-7 and T-47D, and hormone-independent: MDA-MB-231 and MDA-MB-468, human breast cancer cells. The expression of this mRNA is significantly higher in the MDA-MB-468 cells and a correlation of this mRNA expression with the enzymatic activity was observed. The progestin Promegestone (R-5020) at a low concentration (5 x 10(-7) M) can significantly increase the estrogen sulfotransferase activity and its mRNA in the hormone-dependent MCF-7 and T-47D cells. As estrogen sulfates are biologically inactive, the stimulatory effect on sulfotransferase by Promegestone may open attractive possibilities in the control of estradiol in human breast cancer.
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transformation of estrone and estradiol in hormone dependent and hormone independent human breast cancer cells effects of the antiestrogen ici 164 384 danazol and Promegestone r 5020
Breast Cancer Research and Treatment, 1995Co-Authors: Bachlien Nguyen, G Chetrite, J R PasqualiniAbstract:Using different hormone-dependent (MCF-7, T-47D) and hormone-independent (MDA-MB-231, Hs-578S, MDA-MB-436) human breast cancer cells, the interconversion estrone (E1) ⇌ estradiol (E2) was explored. The data show very clearly that in the hormone-dependent cells the tendency is to form E2 after incubation with E1, whereas after incubation with E2 most of this estrogen remains unchanged. In the hormone-independent cells, in contrast most of E1 remains E1, while E2 is converted into E1. The tendency of the reductive ⇌ oxidative direction is supported by the analysis of estrogens in the culture medium. To explore the possible action of different drugs on the 17β-hydroxysteroid dehydrogenase (17β-HSD) activity, it was observed that the potent antiestrogen ICI 164,384 inhibits the conversion of E1 to E2, while a lesser effect is observed with Danazol and only weak inhibition is obtained with the progestagen Promegestone (R-5020). It is concluded that the orientation of 17β-HSD activity for the interconversion E1 ⇌ E2 in hormone-dependent and -independent cells is related to the hormonal status of the cells.
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effect of the progestagen Promegestone r 5020 on mrna of the oestrone sulphatase in the mcf 7 human mammary cancer cells
Anticancer Research, 1994Co-Authors: J R Pasqualini, C Maloche, M Maroni, G ChetriteAbstract:: Using reverse transcriptase polymerase chain reaction amplification it was possible to detect the presence of oestrogen sulphatase mRNA in different hormone-dependent (MCF-7, T-47D) and hormone-independent (MDA-MB-231, MDA-MB-468) mammary cancer cell lines. The expression of this mRNA is significantly higher in T-47D and MDA-MB-231 than in the other cell lines, and a correlation of this expression with the enzymatic activities was observed. The progestagen Promegestone (R-5020) can significantly decrease the mRNA of the sulphatase in MCF-7 cells. As this progestagen can also inhibit the enzyme itself in the same mammary cancer cell line, it is suggested that for the decrease in the sulphatase activity not only the effect on the enzyme, but also the effect on transcriptional factor(s) which express this enzyme are involved. The present data not only contribute to the knowledge of the mechanism of the sulphatase activity, but also can open new possibilities in breast cancer treatment.
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effect of Promegestone tamoxifen 4 hydroxytamoxifen and ici 164 384 on the oestrone sulphatase activity of human breast cancer cells
Anticancer Research, 1993Co-Authors: G Chetrite, L Delalonde, C Varin, J R PasqualiniAbstract:In the present study, we explored the effects on sulphatase activity by Promegestone (R-5020), Tamoxifen (TAM), 4-hydroxytamoxifen (4-OH-TAM) and ICI 164,384 in the T-47D hormone-dependent and MDA-MB-231 hormone-independent mammary cancer cell lines. Using homogenates of these cells it was observed that Promegestone has a significant effect on the inhibition of oestrone (E1) sulphatase activity. As this effect is competitive, it is suggested that there is a direct action of this compound on the enzyme. Tamoxifen has very little or no effect, 4-hydroxytamoxifen has an intermediate effect and ICI 164,384 is active in the enzyme inhibition, particularly with MDA-MB-231 cells. The present data could open new possibilities for human breast cancer treatment, as sulphatase is very active in the first step of the conversion of oestrone sulphate (E1S) to oestradiol (E2), and oestradiol is one of the principal carcinogenic factors in human hormone-dependent breast cancer.
Bachlien Nguyen - One of the best experts on this subject based on the ideXlab platform.
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estrone sulfate sulfatase and 17β hydroxysteroid dehydrogenase activities a hypothesis for their role in the evolution of human breast cancer from hormone dependence to hormone independence
The Journal of Steroid Biochemistry and Molecular Biology, 1995Co-Authors: J R Pasqualini, Bachlien Nguyen, C Maloche, L Delalonde, Marwa Talbi, M C Feinstein, Joaquin Botella, Catherine Blacker, Gérard Chetrite, J. ParisAbstract:Abstract The evaluation of estrogens (estrone, estradiol, and their sulfates) in the breast tissue of post-menopausal patients with breast cancer indicates high levels, particularly of estrone sulfate (E 1 S) which is 15–25 times higher than in the plasma. Breast cancer tissue contains the enzymes necessary for local synthesis of estradiol and it was demonstrated that, despite the presence of the sulfatase and its messenger in hormone-dependent and hormone-independent breast cancer cells, this enzyme operates particularly in hormone-dependent cells. Different progestins: Nomegestrol acetate, Promegestone, progesterone, as well as Danazol, can block the conversion of E 1 S to E 2 very strongly in hormone-dependent breast cancer cells. The last step in the formation of estradiol is the conversion of E 1 to this estrogen by the action of 17β-hydroxysteroid dehydrogenase. This activity is preferentially in the reductive direction (formation of E 2 ) in hormone-dependent cells, but oxidative (E 2 → E 1 ) in hormone-independent cells. Using intact hormone-dependent cells it was observed that Nomegestrol acetate can block the conversion of E 1 to E 2 . It is concluded, firstly, that in addition to ER mutants other factors are involved in the transformation of hormone-dependent breast cancer to hormone-independent, this concerns the enzymatic activity in the formation of E 2 ; it is suggested that stimulatory or repressive factor(s) involved in the enzyme activity are implicated as the cancer evolves to hormone-independence; secondly, different drugs can block the conversion of E 1 S to E 2 . Clinical trials of these “anti-enzyme” substances in breast cancer patients could be the next step to investigate new therapeutic possibilities for this disease.
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transformation of estrone and estradiol in hormone dependent and hormone independent human breast cancer cells effects of the antiestrogen ici 164 384 danazol and Promegestone r 5020
Breast Cancer Research and Treatment, 1995Co-Authors: Bachlien Nguyen, G Chetrite, J R PasqualiniAbstract:Using different hormone-dependent (MCF-7, T-47D) and hormone-independent (MDA-MB-231, Hs-578S, MDA-MB-436) human breast cancer cells, the interconversion estrone (E1) ⇌ estradiol (E2) was explored. The data show very clearly that in the hormone-dependent cells the tendency is to form E2 after incubation with E1, whereas after incubation with E2 most of this estrogen remains unchanged. In the hormone-independent cells, in contrast most of E1 remains E1, while E2 is converted into E1. The tendency of the reductive ⇌ oxidative direction is supported by the analysis of estrogens in the culture medium. To explore the possible action of different drugs on the 17β-hydroxysteroid dehydrogenase (17β-HSD) activity, it was observed that the potent antiestrogen ICI 164,384 inhibits the conversion of E1 to E2, while a lesser effect is observed with Danazol and only weak inhibition is obtained with the progestagen Promegestone (R-5020). It is concluded that the orientation of 17β-HSD activity for the interconversion E1 ⇌ E2 in hormone-dependent and -independent cells is related to the hormonal status of the cells.
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effect of the progestagen r5020 Promegestone and of progesterone on the uptake and on the transformation of estrone sulfate in the mcf 7 and t 47d human mammary cancer cells correlation with progesterone receptor levels
Cancer Letters, 1992Co-Authors: Jorge R. Pasqualini, Claire Varin, Bachlien NguyenAbstract:In the present study we have explored the actions of the progestagen R5020 (Promegestone: 17 alpha, 21-dimethyl-19-nor-pregna-4, 9-diene-3,20-dione) and progesterone on the uptake of [3H]estrone sulfate ([3H]E1S) and its conversion to estradiol (E2) by two hormone-dependent mammary cancer cell lines: MCF-7 and T-47D. R5020 or progesterone significantly decreased the uptake of [3H]E1 and its conversion to (E2). In the cells of the two lines, R5020 or progesterone (5 x 10(-6) M) decreased the E2 concentrations by 2-3 times in relation to the levels in untreated cells. E1S (1 x 10(-7) M) also increased expression of the progesterone receptor (PR) and both R5020 (5 x 10(-6) M) and progesterone (5 x 10(-6) M) blocked this stimulatory action of E1S in cells of both cell lines. As E2 is one of the main factors of cancerization in the breast and estrone sulfate is quantitatively the most important precursor of E2 in this tissue, the decrease of E2 by these progestagens could open new possibilities for the control of E2 in the breast cancer tissue.
Genevieve Panaye - One of the best experts on this subject based on the ideXlab platform.
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inhibition of growth and induction of apoptosis by androgens of a variant of lncap cell line
The Journal of Steroid Biochemistry and Molecular Biology, 2000Co-Authors: Marieodile Jolypharaboz, Laurence Michelcalemard, Jacqueline Chantepie, A M Roch, Alain Ruffion, Jean Andre, B Nicolas, Genevieve PanayeAbstract:Abstract Here are described the effects of androgens, and other molecules known to bind to androgen receptors (AR), on MOP cells established from the human prostate cancer cell line LNCaP. MOP cells contained AR: 100 000 binding sites/cell, KD for 5α dihydrotestosterone (DHT) 0.5 nM, size 110 kDa. The AR gene has the same repetition polymorphism in exon 1 and the T876A mutation in exon 8 as LNCaP. The proliferation of MOP cells in culture was repressed by the synthetic androgen 17β-hydroxy-17-methyl-estra-4,9,11-trien-3-one (R 1881), the antiandrogen cyproterone acetate (CYPA), estradiol (E2), progesterone and the synthetic progestin Promegestone: 17,21 dimethyl-19 nor-4,9 pregnandiene-3,20 dione (R 5020). The number of cells recovered after 7 days decreased to ≈40% of controls. ED70s ranged between 50 pM for R 1881 to 50 nM for E2 and CYPA. Treatment with R 1881 decreased [3H]thymidine incorporation into DNA and increased dramatically the doubling time. R 1881, CYPA and E2 blocked the cell cycle between G1 and S phases and they induced apototosis as demonstrated by the increase of blebs on the plasma membrane, nuclear fragmentation, TdT-mediated dUTP nick end-labeling (TUNEL)-positive cells and internucleosomal DNA breaks. In athymic nude mice, testosterone enanthate prevented the growth of MOP tumors and, when tumors did develop, brought about regression. However, the tumors did not regress completely and finally escaped treatment. In conclusion, a variant of the LNCaP cell line has been established. With these cells it was possible to confirm that androgens paradoxically repress the growth of some prostate cancer cells both in culture and in vivo. In addition it is demonstrated in culture but not in vivo, for the first time to the authors’ knowledge, that a synthetic androgen is able to induce apoptosis of cells established from human prostate carcinoma.
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inhibition of growth and induction of apoptosis by androgens of a variant of lncap cell line
The Journal of Steroid Biochemistry and Molecular Biology, 2000Co-Authors: Marieodile Jolypharaboz, Laurence Michelcalemard, Jacqueline Chantepie, A M Roch, Alain Ruffion, Jean Andre, B Nicolas, Genevieve PanayeAbstract:Abstract Here are described the effects of androgens, and other molecules known to bind to androgen receptors (AR), on MOP cells established from the human prostate cancer cell line LNCaP. MOP cells contained AR: 100 000 binding sites/cell, KD for 5α dihydrotestosterone (DHT) 0.5 nM, size 110 kDa. The AR gene has the same repetition polymorphism in exon 1 and the T876A mutation in exon 8 as LNCaP. The proliferation of MOP cells in culture was repressed by the synthetic androgen 17β-hydroxy-17-methyl-estra-4,9,11-trien-3-one (R 1881), the antiandrogen cyproterone acetate (CYPA), estradiol (E2), progesterone and the synthetic progestin Promegestone: 17,21 dimethyl-19 nor-4,9 pregnandiene-3,20 dione (R 5020). The number of cells recovered after 7 days decreased to ≈40% of controls. ED70s ranged between 50 pM for R 1881 to 50 nM for E2 and CYPA. Treatment with R 1881 decreased [3H]thymidine incorporation into DNA and increased dramatically the doubling time. R 1881, CYPA and E2 blocked the cell cycle between G1 and S phases and they induced apototosis as demonstrated by the increase of blebs on the plasma membrane, nuclear fragmentation, TdT-mediated dUTP nick end-labeling (TUNEL)-positive cells and internucleosomal DNA breaks. In athymic nude mice, testosterone enanthate prevented the growth of MOP tumors and, when tumors did develop, brought about regression. However, the tumors did not regress completely and finally escaped treatment. In conclusion, a variant of the LNCaP cell line has been established. With these cells it was possible to confirm that androgens paradoxically repress the growth of some prostate cancer cells both in culture and in vivo. In addition it is demonstrated in culture but not in vivo, for the first time to the authors’ knowledge, that a synthetic androgen is able to induce apoptosis of cells established from human prostate carcinoma.
Jean Andre - One of the best experts on this subject based on the ideXlab platform.
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inhibition of growth and induction of apoptosis by androgens of a variant of lncap cell line
The Journal of Steroid Biochemistry and Molecular Biology, 2000Co-Authors: Marieodile Jolypharaboz, Laurence Michelcalemard, Jacqueline Chantepie, A M Roch, Alain Ruffion, Jean Andre, B Nicolas, Genevieve PanayeAbstract:Abstract Here are described the effects of androgens, and other molecules known to bind to androgen receptors (AR), on MOP cells established from the human prostate cancer cell line LNCaP. MOP cells contained AR: 100 000 binding sites/cell, KD for 5α dihydrotestosterone (DHT) 0.5 nM, size 110 kDa. The AR gene has the same repetition polymorphism in exon 1 and the T876A mutation in exon 8 as LNCaP. The proliferation of MOP cells in culture was repressed by the synthetic androgen 17β-hydroxy-17-methyl-estra-4,9,11-trien-3-one (R 1881), the antiandrogen cyproterone acetate (CYPA), estradiol (E2), progesterone and the synthetic progestin Promegestone: 17,21 dimethyl-19 nor-4,9 pregnandiene-3,20 dione (R 5020). The number of cells recovered after 7 days decreased to ≈40% of controls. ED70s ranged between 50 pM for R 1881 to 50 nM for E2 and CYPA. Treatment with R 1881 decreased [3H]thymidine incorporation into DNA and increased dramatically the doubling time. R 1881, CYPA and E2 blocked the cell cycle between G1 and S phases and they induced apototosis as demonstrated by the increase of blebs on the plasma membrane, nuclear fragmentation, TdT-mediated dUTP nick end-labeling (TUNEL)-positive cells and internucleosomal DNA breaks. In athymic nude mice, testosterone enanthate prevented the growth of MOP tumors and, when tumors did develop, brought about regression. However, the tumors did not regress completely and finally escaped treatment. In conclusion, a variant of the LNCaP cell line has been established. With these cells it was possible to confirm that androgens paradoxically repress the growth of some prostate cancer cells both in culture and in vivo. In addition it is demonstrated in culture but not in vivo, for the first time to the authors’ knowledge, that a synthetic androgen is able to induce apoptosis of cells established from human prostate carcinoma.
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inhibition of growth and induction of apoptosis by androgens of a variant of lncap cell line
The Journal of Steroid Biochemistry and Molecular Biology, 2000Co-Authors: Marieodile Jolypharaboz, Laurence Michelcalemard, Jacqueline Chantepie, A M Roch, Alain Ruffion, Jean Andre, B Nicolas, Genevieve PanayeAbstract:Abstract Here are described the effects of androgens, and other molecules known to bind to androgen receptors (AR), on MOP cells established from the human prostate cancer cell line LNCaP. MOP cells contained AR: 100 000 binding sites/cell, KD for 5α dihydrotestosterone (DHT) 0.5 nM, size 110 kDa. The AR gene has the same repetition polymorphism in exon 1 and the T876A mutation in exon 8 as LNCaP. The proliferation of MOP cells in culture was repressed by the synthetic androgen 17β-hydroxy-17-methyl-estra-4,9,11-trien-3-one (R 1881), the antiandrogen cyproterone acetate (CYPA), estradiol (E2), progesterone and the synthetic progestin Promegestone: 17,21 dimethyl-19 nor-4,9 pregnandiene-3,20 dione (R 5020). The number of cells recovered after 7 days decreased to ≈40% of controls. ED70s ranged between 50 pM for R 1881 to 50 nM for E2 and CYPA. Treatment with R 1881 decreased [3H]thymidine incorporation into DNA and increased dramatically the doubling time. R 1881, CYPA and E2 blocked the cell cycle between G1 and S phases and they induced apototosis as demonstrated by the increase of blebs on the plasma membrane, nuclear fragmentation, TdT-mediated dUTP nick end-labeling (TUNEL)-positive cells and internucleosomal DNA breaks. In athymic nude mice, testosterone enanthate prevented the growth of MOP tumors and, when tumors did develop, brought about regression. However, the tumors did not regress completely and finally escaped treatment. In conclusion, a variant of the LNCaP cell line has been established. With these cells it was possible to confirm that androgens paradoxically repress the growth of some prostate cancer cells both in culture and in vivo. In addition it is demonstrated in culture but not in vivo, for the first time to the authors’ knowledge, that a synthetic androgen is able to induce apoptosis of cells established from human prostate carcinoma.
