title: Combined effects of terazosin and genistein on a metastatic, hormone-independent human prostate cancer cell line.
abstract: Metastatic prostate cancer progresses from androgen-dependent to androgen-independent. Terazosin, a long-acting selective alpha1-adrenoreceptor antagonist, induces apoptosis of prostate cancer cells in an alpha1-adrenoreceptor-independent manner, while genistein, a major soy isoflavone, inhibits the growth of several types of cancer cells. The present study was designed to test the therapeutic potential of a combination of terazosin and genistein using a metastatic, hormone-independent prostatic cancer cell line, DU-145. Terazosin or genistein treatment inhibited the growth of DU-145 cells in a dose-dependent manner, whereas had no effect on normal prostate epithelial cells. Addition of 1 microg/ml of terazosin, which was inactive alone, augmented the growth inhibitory effect of 5 microg/ml of genistein. Co-treatment with terazosin resulted in the genistein-induced arrest of DU-145 cells in G2/M phase being overridden and an increase in apoptotic cells, as evidenced by procaspase-3 activation and PARP cleavage. The combination also caused a greater decrease in the levels of the apoptosis-regulating protein, Bcl-XL, and of VEGF165 and VEGF121 than genistein alone. In conclusion, the terazosin/genistein combination was more effective in inhibiting cell growth and VEGF expression as well as inducing apoptosis of the metastatic, androgen-independent prostate cancer cell line, DU-145, than either alone. The doses used in this study are in lower and nontoxic anticancer dosage range, suggesting this combination has potential for therapeutic use.
authors.affiliation: Department of Biochemistry, College of Medicine, Kaohsiung Medical University, Kaohsiung 80708, Taiwan.
authors.forename: Kee-Lung
authors.initials: KL
authors.lastname: Chang
authors.forename: Hsiao-Ling
authors.initials: HL
authors.lastname: Cheng
authors.forename: Li-Wen
authors.initials: LW
authors.lastname: Huang
authors.forename: Bau-Shan
authors.initials: BS
authors.lastname: Hsieh
authors.forename: Yu-Chen
authors.initials: YC
authors.lastname: Hu
authors.forename: Tsai-Tung
authors.initials: TT
authors.lastname: Chih
authors.forename: Huey-Wen
authors.initials: HW
authors.lastname: Shyu
authors.forename: Shu-Jem
authors.initials: SJ
authors.lastname: Su
mesh_terms: D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D015153:Blotting, Western; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D005434:Flow Cytometry; D019833:Genistein / Q000008:administration & dosage; D006801:Humans; D020287:In Situ Nick-End Labeling; D008297:Male; D008856:Microscopy, Fluorescence; D011224:Prazosin / Q000008:administration & dosage / Q000031:analogs & derivatives; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000473:pathology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D042461:Vascular Endothelial Growth Factor A / Q000187:drug effects / Q000378:metabolism
chemical_list: D042461:Vascular Endothelial Growth Factor A; C041226:Terazosin; D019833:Genistein; D011224:Prazosin