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Inhibition of telomerase activity and secretion of prostate specific antigen by silibinin in prostate cancer cells.
J Urol 2004; 171(5):1934-8JU

Abstract

PURPOSE

The androgen sensitive prostate cancer cell line LNCaP is strongly positive for dihydrotestosterone (DHT) dependent telomerase activity, which is an important factor in cellular immortality and carcinogenesis. In this study we determined the potential of silibinin as an anticancer drug that down-regulates telomerase activity and prostate specific antigen (PSA) together with the co-activator of the androgen receptor prostate epithelium specific Ets transcription factor.

MATERIALS AND METHODS

LNCaP cells were treated with various concentrations of silibinin in the presence or absence of 5alpha-DHT. We used real-time reverse transcriptase-polymerase chain reaction to quantify mRNA expression of PSA, prostate epithelium specific Ets transcription factor and the catalytic subunit of telomerase vs the housekeeping gene porphobilinogen deaminase with gene specific, dual labeled fluorescence probes. PSA secretion from LNCaP cells in conditioned medium was measured with an Elecsys System 2010 (Roche Diagnostics, Mannheim, Germany) and telomerase activity in extracts from LNCaP cells was measured with a TRAP (telomeric repeat amplification protocol) assay.

RESULTS

Silibinin down-regulated PSA mRNA expression and PSA secretion in conditioned medium. Simultaneous stimulation with silibinin and 10(-8) M DHT also resulted in PSA down-regulation, whereas DHT alone increased PSA secretion. Telomerase catalytic subunit mRNA decreased significantly after silibinin stimulation. Telomerase activity was down-regulated by silibinin and stimulated by DHT. The 2 agents in combination resulted in telomerase down-regulation.

CONCLUSIONS

The down-regulation of PSA by silibinin and its counteraction on DHT effects indicate that this compound can interact with the expression of genes that are regulated through the androgen receptor. Silibinin can also inhibit the telomerase activity that mediates cell immortality and carcinogenesis. The 2 effects underline the possible therapeutic use of silibinin as an antiproliferative agent in intervention for prostate cancer.

Authors+Show Affiliations

Department of Urology, Institute of Human Genetics, Georg-August-University, Göttingen, Germany.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

15076315

Citation

Thelen, P, et al. "Inhibition of Telomerase Activity and Secretion of Prostate Specific Antigen By Silibinin in Prostate Cancer Cells." The Journal of Urology, vol. 171, no. 5, 2004, pp. 1934-8.
Thelen P, Wuttke W, Jarry H, et al. Inhibition of telomerase activity and secretion of prostate specific antigen by silibinin in prostate cancer cells. J Urol. 2004;171(5):1934-8.
Thelen, P., Wuttke, W., Jarry, H., Grzmil, M., & Ringert, R. H. (2004). Inhibition of telomerase activity and secretion of prostate specific antigen by silibinin in prostate cancer cells. The Journal of Urology, 171(5), pp. 1934-8.
Thelen P, et al. Inhibition of Telomerase Activity and Secretion of Prostate Specific Antigen By Silibinin in Prostate Cancer Cells. J Urol. 2004;171(5):1934-8. PubMed PMID: 15076315.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Inhibition of telomerase activity and secretion of prostate specific antigen by silibinin in prostate cancer cells. AU - Thelen,P, AU - Wuttke,W, AU - Jarry,H, AU - Grzmil,M, AU - Ringert,R-H, PY - 2004/4/13/pubmed PY - 2004/5/7/medline PY - 2004/4/13/entrez SP - 1934 EP - 8 JF - The Journal of urology JO - J. Urol. VL - 171 IS - 5 N2 - PURPOSE: The androgen sensitive prostate cancer cell line LNCaP is strongly positive for dihydrotestosterone (DHT) dependent telomerase activity, which is an important factor in cellular immortality and carcinogenesis. In this study we determined the potential of silibinin as an anticancer drug that down-regulates telomerase activity and prostate specific antigen (PSA) together with the co-activator of the androgen receptor prostate epithelium specific Ets transcription factor. MATERIALS AND METHODS: LNCaP cells were treated with various concentrations of silibinin in the presence or absence of 5alpha-DHT. We used real-time reverse transcriptase-polymerase chain reaction to quantify mRNA expression of PSA, prostate epithelium specific Ets transcription factor and the catalytic subunit of telomerase vs the housekeeping gene porphobilinogen deaminase with gene specific, dual labeled fluorescence probes. PSA secretion from LNCaP cells in conditioned medium was measured with an Elecsys System 2010 (Roche Diagnostics, Mannheim, Germany) and telomerase activity in extracts from LNCaP cells was measured with a TRAP (telomeric repeat amplification protocol) assay. RESULTS: Silibinin down-regulated PSA mRNA expression and PSA secretion in conditioned medium. Simultaneous stimulation with silibinin and 10(-8) M DHT also resulted in PSA down-regulation, whereas DHT alone increased PSA secretion. Telomerase catalytic subunit mRNA decreased significantly after silibinin stimulation. Telomerase activity was down-regulated by silibinin and stimulated by DHT. The 2 agents in combination resulted in telomerase down-regulation. CONCLUSIONS: The down-regulation of PSA by silibinin and its counteraction on DHT effects indicate that this compound can interact with the expression of genes that are regulated through the androgen receptor. Silibinin can also inhibit the telomerase activity that mediates cell immortality and carcinogenesis. The 2 effects underline the possible therapeutic use of silibinin as an antiproliferative agent in intervention for prostate cancer. SN - 0022-5347 UR - https://www.unboundmedicine.com/medline/citation/15076315/Inhibition_of_telomerase_activity_and_secretion_of_prostate_specific_antigen_by_silibinin_in_prostate_cancer_cells_ L2 - https://www.jurology.com/doi/full/10.1097/01.ju.0000121329.37206.1b?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub=pubmed DB - PRIME DP - Unbound Medicine ER -