Combined effects of terazosin and genistein on a metastatic, hormone-independent human prostate cancer cell line.
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.
Chang
Kee-Lung
KL
Department of Biochemistry, College of Medicine, Kaohsiung Medical University, Kaohsiung 80708, Taiwan.
Cheng
Hsiao-Ling
HL
Huang
Li-Wen
LW
Hsieh
Bau-Shan
BS
Hu
Yu-Chen
YC
Chih
Tsai-Tung
TT
Shyu
Huey-Wen
HW
Su
Shu-Jem
SJ
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
D042461:Vascular Endothelial Growth Factor A; C041226:Terazosin; D019833:Genistein; D011224:Prazosin