The synthetic estrogen diethylstilbestrol (DES) inhibits the telomerase activity and gene expression of prostate cancer cells.

Telomerase, which lengthens telomeres, is normally down-regulated in somatic cells and highly up-regulated in dividing cells, such as malignant cells. Human prostate cancer is androgen dependent. Estrogens, including the synthetic estrogen diethylstilbestrol (DES), are used in prostate cancer treatment to reduce androgen levels via feedback inhibition of the hypothalamic release of luteinizing hormone releasing hormone (LH-RH). DES has also direct anticancer activities, such as apoptosis induction. We investigated in vitro the effect of DES on telomerase activity and on gene expression in the presence and absence of androgens. We used two prostate cancer cell lines: LNCaP (androgen dependent) and PC3 (androgen independent). LNCaP and PC3 cells were treated with 0.1-1,000 nM testosterone or dihydrotestosterone (DHT) in the presence of DES (25 or 50 microM). Cell telomerase activity and gene expression (mRNA) were measured. LNCaP: As expected, testosterone and DHT significantly increased telomerase activity and gene expression. However, these effects were inhibited by DES. Contrary to expectations, the combination of DES and testosterone functioned synergistically leading to complete inhibition of telomerase activity. PC3: Testosterone and DHT did not affect telomerase activity and gene expression, whereas DES, in the absence or presence of the androgens, significantly inhibited telomerase activity. In the present study, we demonstrated the ability of DES to inhibit telomerase in prostate cancer cells. Androgens did not limit the inhibitory effect and even acted synergistically with DES in the LNCaP line. This phenomenon should be considered if telomerase inhibition is part of prostate cancer treatment.

Geier R ，Adler S ，Rashid G ，Klein A ... -  《-》

Indole-3-carbinol inhibits telomerase activity and gene expression in prostate cancer cell lines.

Adler S ，Rashid G ，Klein A 《-》

Inhibition of telomerase activity and secretion of prostate specific antigen by silibinin in prostate cancer cells.

Thelen P ，Wuttke W ，Jarry H ，Grzmil M ，Ringert RH ... -  《JOURNAL OF UROLOGY》

Liprin-alpha2 gene, protein tyrosine phosphatase LAR interacting protein related gene, is downregulated by androgens in the human prostate cancer cell line LNCaP.

Fujinami K ，Uemura H ，Ishiguro H ，Kubota Y ... -  《INTERNATIONAL JOURNAL OF MOLECULAR MEDICINE》

Bone extracellular matrix induces homeobox proteins independent of androgens: possible mechanism for androgen-independent growth in human prostate cancer cells.

Robbins SE ，Shu WP ，Kirschenbaum A ，Levine AC ，Miniati DN ，Liu BC ... -  《PROSTATE》