Bouchal, Jan and Baumforth, Karl R N and Sváchová, Michaela and Murray, Paul G and Angerer, Erwin von and Kolár, Zdenek (2005) Microarray analysis of bicalutamide action on telomerase activity, p53 pathway and viability of prostate carcinoma cell lines. The Journal of pharmacy and pharmacology 57 (1), pp. 83-92.
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Bicalutamide is a non-steroidal anti-androgen commonly used in the treatment of prostate carcinoma. We analysed the transcriptional response to bicalutamide treatment with the aim of explaining the inhibition of telomerase in the androgen-sensitive cell line LNCaP and the effects of bicalutamide on the androgen-insensitive cell line DU145. Cells treated with 80 muM bicalutamide in steroid-depleted medium for 1 day were analysed in duplicate by Affymetrix Human Genome Focus Arrays. Response to bicalutamide in LNCaP cells was represented by downregulation of androgen-regulated genes, activation of the p53 pathway and inhibition of telomerase, which was associated with downregulation of v-myc avian myelocytomatosis viral oncogene homologue (MYC) and telomerase reverse transcriptase subunit. In DU145 cells we observed the influence of cell density on bicalutamide effectivity such that highly confluent cells showed lesser sensitivity than low confluent ones. In conclusion, we provide an explanation for telomerase inhibition after androgen receptor blockade in LNCaP cells and we also report activation of the p53 pathway in LNCaP cells and in-vitro sensitivity to bicalutamide of low confluent androgen-insensitive DU145 cells. These findings might have implications for both experimental and clinical research into prostate cancer. In particular, activation of the p53 pathway after treatment with 80 microM bicalutamide could justify usage of bicalutamide dosages higher than 150 mg daily in androgen-sensitive carcinoma therapy.
|Institutions:||Chemistry and Pharmacy > Institute of Pharmacy > Pharmaceutical/Medicinal Chemistry II (Prof. Buschauer)|
|Subjects:||500 Science > 570 Life sciences|
500 Science > 540 Chemistry & allied sciences
600 Technology > 610 Medical sciences Medicine
|Refereed:||Yes, this version has been refereed|
|Created at the University of Regensburg:||Partially|
|Owner:||Prof. Armin Buschauer|
|Deposited On:||04 Nov 2008 15:48|
|Last Modified:||05 Aug 2009 13:48|