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Repositioning Dopamine D2 Receptor Agonist Bromocriptine to Enhance Docetaxel Chemotherapy and Treat Bone Metastatic Prostate Cancer
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| Zeitschriftentitel: | Molecular Cancer Therapeutics |
|---|---|
| Personen und Körperschaften: | , , , , , , , , |
| In: | Molecular Cancer Therapeutics, 17, 2018, 9, S. 1859-1870 |
| Format: | E-Article |
| Sprache: | Englisch |
| veröffentlicht: |
American Association for Cancer Research (AACR)
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| Schlagwörter: |
| author_facet |
Yang, Yang Mamouni, Kenza Li, Xin Chen, Yanhua Kavuri, Sravan Du, Yuhong Fu, Haian Kucuk, Omer Wu, Daqing Yang, Yang Mamouni, Kenza Li, Xin Chen, Yanhua Kavuri, Sravan Du, Yuhong Fu, Haian Kucuk, Omer Wu, Daqing |
|---|---|
| author |
Yang, Yang Mamouni, Kenza Li, Xin Chen, Yanhua Kavuri, Sravan Du, Yuhong Fu, Haian Kucuk, Omer Wu, Daqing |
| spellingShingle |
Yang, Yang Mamouni, Kenza Li, Xin Chen, Yanhua Kavuri, Sravan Du, Yuhong Fu, Haian Kucuk, Omer Wu, Daqing Molecular Cancer Therapeutics Repositioning Dopamine D2 Receptor Agonist Bromocriptine to Enhance Docetaxel Chemotherapy and Treat Bone Metastatic Prostate Cancer Cancer Research Oncology |
| author_sort |
yang, yang |
| spelling |
Yang, Yang Mamouni, Kenza Li, Xin Chen, Yanhua Kavuri, Sravan Du, Yuhong Fu, Haian Kucuk, Omer Wu, Daqing 1535-7163 1538-8514 American Association for Cancer Research (AACR) Cancer Research Oncology http://dx.doi.org/10.1158/1535-7163.mct-17-1176 <jats:title>Abstract</jats:title> <jats:p>Docetaxel resistance remains a major obstacle in the treatment of prostate cancer bone metastasis. In this study, we demonstrate that the dopamine D2 receptor (DRD2) agonist bromocriptine effectively enhances docetaxel efficacy and suppresses skeletal growth of prostate cancer in preclinical models. DRD2 is ubiquitously expressed in prostate cancer cell lines and significantly reduced in prostate cancer tissues with high Gleason score. Bromocriptine has weak to moderate cytotoxicity in prostate cancer cells, but effectively induces cell-cycle arrest. At the molecular level, bromocriptine inhibits the expression of c-Myc, E2F-1, and survivin and increases the expression of p53, p21, and p27. Intriguingly, bromocriptine markedly reduces androgen receptor levels, partially through Hsp90-mediated protein degradation. The combination of bromocriptine and docetaxel demonstrates enhanced in vitro cytotoxicity in prostate cancer cells and significantly retards the skeletal growth of C4-2-Luc tumors in mice. Collectively, these results provide the first experimental evidence for repurposing bromocriptine as an effective adjunct therapy to enhance docetaxel efficacy in prostate cancer. Mol Cancer Ther; 17(9); 1859–70. ©2018 AACR.</jats:p> Repositioning Dopamine D2 Receptor Agonist Bromocriptine to Enhance Docetaxel Chemotherapy and Treat Bone Metastatic Prostate Cancer Molecular Cancer Therapeutics |
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| title |
Repositioning Dopamine D2 Receptor Agonist Bromocriptine to Enhance Docetaxel Chemotherapy and Treat Bone Metastatic Prostate Cancer |
| title_unstemmed |
Repositioning Dopamine D2 Receptor Agonist Bromocriptine to Enhance Docetaxel Chemotherapy and Treat Bone Metastatic Prostate Cancer |
| title_full |
Repositioning Dopamine D2 Receptor Agonist Bromocriptine to Enhance Docetaxel Chemotherapy and Treat Bone Metastatic Prostate Cancer |
| title_fullStr |
Repositioning Dopamine D2 Receptor Agonist Bromocriptine to Enhance Docetaxel Chemotherapy and Treat Bone Metastatic Prostate Cancer |
| title_full_unstemmed |
Repositioning Dopamine D2 Receptor Agonist Bromocriptine to Enhance Docetaxel Chemotherapy and Treat Bone Metastatic Prostate Cancer |
| title_short |
Repositioning Dopamine D2 Receptor Agonist Bromocriptine to Enhance Docetaxel Chemotherapy and Treat Bone Metastatic Prostate Cancer |
| title_sort |
repositioning dopamine d2 receptor agonist bromocriptine to enhance docetaxel chemotherapy and treat bone metastatic prostate cancer |
| topic |
Cancer Research Oncology |
| url |
http://dx.doi.org/10.1158/1535-7163.mct-17-1176 |
| publishDate |
2018 |
| physical |
1859-1870 |
| description |
<jats:title>Abstract</jats:title>
<jats:p>Docetaxel resistance remains a major obstacle in the treatment of prostate cancer bone metastasis. In this study, we demonstrate that the dopamine D2 receptor (DRD2) agonist bromocriptine effectively enhances docetaxel efficacy and suppresses skeletal growth of prostate cancer in preclinical models. DRD2 is ubiquitously expressed in prostate cancer cell lines and significantly reduced in prostate cancer tissues with high Gleason score. Bromocriptine has weak to moderate cytotoxicity in prostate cancer cells, but effectively induces cell-cycle arrest. At the molecular level, bromocriptine inhibits the expression of c-Myc, E2F-1, and survivin and increases the expression of p53, p21, and p27. Intriguingly, bromocriptine markedly reduces androgen receptor levels, partially through Hsp90-mediated protein degradation. The combination of bromocriptine and docetaxel demonstrates enhanced in vitro cytotoxicity in prostate cancer cells and significantly retards the skeletal growth of C4-2-Luc tumors in mice. Collectively, these results provide the first experimental evidence for repurposing bromocriptine as an effective adjunct therapy to enhance docetaxel efficacy in prostate cancer. Mol Cancer Ther; 17(9); 1859–70. ©2018 AACR.</jats:p> |
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| author | Yang, Yang, Mamouni, Kenza, Li, Xin, Chen, Yanhua, Kavuri, Sravan, Du, Yuhong, Fu, Haian, Kucuk, Omer, Wu, Daqing |
| author_facet | Yang, Yang, Mamouni, Kenza, Li, Xin, Chen, Yanhua, Kavuri, Sravan, Du, Yuhong, Fu, Haian, Kucuk, Omer, Wu, Daqing, Yang, Yang, Mamouni, Kenza, Li, Xin, Chen, Yanhua, Kavuri, Sravan, Du, Yuhong, Fu, Haian, Kucuk, Omer, Wu, Daqing |
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| description | <jats:title>Abstract</jats:title> <jats:p>Docetaxel resistance remains a major obstacle in the treatment of prostate cancer bone metastasis. In this study, we demonstrate that the dopamine D2 receptor (DRD2) agonist bromocriptine effectively enhances docetaxel efficacy and suppresses skeletal growth of prostate cancer in preclinical models. DRD2 is ubiquitously expressed in prostate cancer cell lines and significantly reduced in prostate cancer tissues with high Gleason score. Bromocriptine has weak to moderate cytotoxicity in prostate cancer cells, but effectively induces cell-cycle arrest. At the molecular level, bromocriptine inhibits the expression of c-Myc, E2F-1, and survivin and increases the expression of p53, p21, and p27. Intriguingly, bromocriptine markedly reduces androgen receptor levels, partially through Hsp90-mediated protein degradation. The combination of bromocriptine and docetaxel demonstrates enhanced in vitro cytotoxicity in prostate cancer cells and significantly retards the skeletal growth of C4-2-Luc tumors in mice. Collectively, these results provide the first experimental evidence for repurposing bromocriptine as an effective adjunct therapy to enhance docetaxel efficacy in prostate cancer. Mol Cancer Ther; 17(9); 1859–70. ©2018 AACR.</jats:p> |
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| imprint_str_mv | American Association for Cancer Research (AACR), 2018 |
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| spelling | Yang, Yang Mamouni, Kenza Li, Xin Chen, Yanhua Kavuri, Sravan Du, Yuhong Fu, Haian Kucuk, Omer Wu, Daqing 1535-7163 1538-8514 American Association for Cancer Research (AACR) Cancer Research Oncology http://dx.doi.org/10.1158/1535-7163.mct-17-1176 <jats:title>Abstract</jats:title> <jats:p>Docetaxel resistance remains a major obstacle in the treatment of prostate cancer bone metastasis. In this study, we demonstrate that the dopamine D2 receptor (DRD2) agonist bromocriptine effectively enhances docetaxel efficacy and suppresses skeletal growth of prostate cancer in preclinical models. DRD2 is ubiquitously expressed in prostate cancer cell lines and significantly reduced in prostate cancer tissues with high Gleason score. Bromocriptine has weak to moderate cytotoxicity in prostate cancer cells, but effectively induces cell-cycle arrest. At the molecular level, bromocriptine inhibits the expression of c-Myc, E2F-1, and survivin and increases the expression of p53, p21, and p27. Intriguingly, bromocriptine markedly reduces androgen receptor levels, partially through Hsp90-mediated protein degradation. The combination of bromocriptine and docetaxel demonstrates enhanced in vitro cytotoxicity in prostate cancer cells and significantly retards the skeletal growth of C4-2-Luc tumors in mice. Collectively, these results provide the first experimental evidence for repurposing bromocriptine as an effective adjunct therapy to enhance docetaxel efficacy in prostate cancer. Mol Cancer Ther; 17(9); 1859–70. ©2018 AACR.</jats:p> Repositioning Dopamine D2 Receptor Agonist Bromocriptine to Enhance Docetaxel Chemotherapy and Treat Bone Metastatic Prostate Cancer Molecular Cancer Therapeutics |
| spellingShingle | Yang, Yang, Mamouni, Kenza, Li, Xin, Chen, Yanhua, Kavuri, Sravan, Du, Yuhong, Fu, Haian, Kucuk, Omer, Wu, Daqing, Molecular Cancer Therapeutics, Repositioning Dopamine D2 Receptor Agonist Bromocriptine to Enhance Docetaxel Chemotherapy and Treat Bone Metastatic Prostate Cancer, Cancer Research, Oncology |
| title | Repositioning Dopamine D2 Receptor Agonist Bromocriptine to Enhance Docetaxel Chemotherapy and Treat Bone Metastatic Prostate Cancer |
| title_full | Repositioning Dopamine D2 Receptor Agonist Bromocriptine to Enhance Docetaxel Chemotherapy and Treat Bone Metastatic Prostate Cancer |
| title_fullStr | Repositioning Dopamine D2 Receptor Agonist Bromocriptine to Enhance Docetaxel Chemotherapy and Treat Bone Metastatic Prostate Cancer |
| title_full_unstemmed | Repositioning Dopamine D2 Receptor Agonist Bromocriptine to Enhance Docetaxel Chemotherapy and Treat Bone Metastatic Prostate Cancer |
| title_short | Repositioning Dopamine D2 Receptor Agonist Bromocriptine to Enhance Docetaxel Chemotherapy and Treat Bone Metastatic Prostate Cancer |
| title_sort | repositioning dopamine d2 receptor agonist bromocriptine to enhance docetaxel chemotherapy and treat bone metastatic prostate cancer |
| title_unstemmed | Repositioning Dopamine D2 Receptor Agonist Bromocriptine to Enhance Docetaxel Chemotherapy and Treat Bone Metastatic Prostate Cancer |
| topic | Cancer Research, Oncology |
| url | http://dx.doi.org/10.1158/1535-7163.mct-17-1176 |