ABSTRACT
BACKGROUND: Indole-3-carbinol (I3C) is a phytochemical with anticarcinogenic properties. Telomerase activity is key in carcinogenesis. We investigated the effect of I3C on telomerase in human prostate cancer cell lines LNCaP and PC3. MATERIALS AND METHODS: Cells were treated with I3C at 100 and 250 µM with and without 10-50 µM diethylstilbestrol (DES). Telomerase activity was performed using TRAPaze Telomerase Detection Kit, and hTERT gene expression by real time quantitative RT-PCR. RESULTS: I3C (250 µM) inhibited telomerase activity and mRNA expression of hTERT in LNCaP and PC3 cells. I3C at 250 µM combined with any concentration of DES was cytotoxic to LNCaP. Telomerase activity in PC3 cells with 250 µM of I3C and 25 or 50 µM of DES was significantly reduced or inhibited, respectively. I3C combined with DES reduced PC3 viability and eliminated LNCaP cells. CONCLUSION: I3C significantly inhibited telomerase activity and hTERT mRNA expression in LNCaP and PC3 cells. Combination of I3C and DES enhanced the inhibitory effect on telomerase activity, gene expression, and cell viability. These results implied that I3C and DES combined might help in prostate cancer treatment.
Subject(s)
Anticarcinogenic Agents/pharmacology , Gene Expression Regulation, Neoplastic/drug effects , Indoles/pharmacology , Prostatic Neoplasms/drug therapy , Prostatic Neoplasms/genetics , Telomerase/antagonists & inhibitors , Diethylstilbestrol/pharmacology , Enzyme-Linked Immunosorbent Assay , Estrogens, Non-Steroidal/pharmacology , Humans , Male , Prostatic Neoplasms/enzymology , RNA, Messenger/genetics , Real-Time Polymerase Chain Reaction , Telomerase/genetics , Telomerase/metabolism , Tumor Cells, CulturedABSTRACT
BACKGROUND: 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). METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.
