Abstract
Androgen deprivation therapy of prostate cancer with estrogens shows significant cardiovascular side-effects. To develop effective prostate cancer therapeutic agent(s) with minimal cardiovascular side-effects, we compared the effects of various estrogen receptor (ER) ligands on the modulation of dihydrotestosterone (DHT) actions in LAPC-4 and LNCaP prostate cancer cells and human aortic endothelial cells (HAECs). DHT stimulated the proliferation of HAEC, LAPC-4 and LNCaP cells and induced PSA mRNA expression in LAPC-4 cells. These DHT actions were differentially modulated by ER ligands in a cell-dependent manner. In LAPC-4 cells, knockdown of ERβ expression partially eliminated the βE2 inhibition of DHT-induced LAPC-4 cell proliferation, and a parallel change was observed between ER ligand modulation of DHT-induced cell proliferation and cyclin A expression. The obtained data suggest that it is feasible to develop effective agent(s) for prostate cancer therapy with minimal cardiovascular side-effects and 17α-estradiol and genistein are such potential agents.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Androgens / pharmacology
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Aorta / cytology*
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Aorta / drug effects
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Aorta / metabolism
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Blotting, Western
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Cell Proliferation / drug effects*
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Cells, Cultured
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Cyclin A
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Dihydrotestosterone / pharmacology*
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Endothelium, Vascular / cytology*
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Endothelium, Vascular / drug effects
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Endothelium, Vascular / metabolism
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Estrogen Receptor alpha / antagonists & inhibitors
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Estrogen Receptor alpha / genetics
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Estrogen Receptor alpha / metabolism*
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Estrogen Receptor beta / antagonists & inhibitors
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Estrogen Receptor beta / genetics
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Estrogen Receptor beta / metabolism*
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Estrogens
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Humans
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Male
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Prostate-Specific Antigen / metabolism
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Prostatic Neoplasms / drug therapy
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Prostatic Neoplasms / metabolism
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Prostatic Neoplasms / pathology*
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RNA, Messenger / genetics
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RNA, Small Interfering / genetics
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Real-Time Polymerase Chain Reaction
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Reverse Transcriptase Polymerase Chain Reaction
Substances
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Androgens
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Cyclin A
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ESR1 protein, human
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Estrogen Receptor alpha
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Estrogen Receptor beta
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Estrogens
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RNA, Messenger
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RNA, Small Interfering
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Dihydrotestosterone
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Prostate-Specific Antigen