Growth Of Human Prostatic Cells Research Articles

Proteolytic Inhibition in Regulating the Insulin-Like Growth Factor-Binding Proteins in Prostate Cancer

Prostate-Specific Antigen (PSA), a serine protease, is believed to regulate the actions of extracellular matrix proteins such as fibronectin and Insulin-like Growth Factor-Binding Proteins (IGFBPs), possible factors involved in tumor progression and metastasis. Two phosphonate ester derivatives Cbz-(4-AmPhGly)p(OPh)2 (Inh I) and Cbz- (4-AmPhe)p(OPh)2 (Inh II), first mechanism-based inhibitors for PSA were synthesized using Oleksyszyn oxidation reaction, and their inhibitory activities on cleaving fibronectin (both human and bovine) and IGFBPs were investigated. To elucidate the role of PSA in the development and progression of prostate cancer, the regulation of the PSA activity on these two physiological substrates was clearly illustrated by modulating the concentrations of inhibitors, i.e. cleavages of both fibronectin and IGFBPs by PSA are inhibited by structure specific designed diphenyl phosphonate esters, consistent with the putative degradation. The inhibition data of two synthetic phosphonate ester derivatives, as lead compounds, will facilitate the development of more specific inhibitors of PSA activity, likely to modulate the physiological control of the IGF in human prostatic cell growth.

Inorganic Polyphosphates: Jack of All Trades

Prostate-Specific Antigen (PSA), a serine protease, is believed to regulate the actions of extracellular matrix proteins such as fibronectin and Insulin-like Growth Factor-Binding Proteins (IGFBPs), possible factors involved in tumor progression and metastasis. Two phosphonate ester derivatives Cbz-(4-AmPhGly)p(OPh)2 (Inh I) and Cbz- (4-AmPhe)p(OPh)2 (Inh II), first mechanism-based inhibitors for PSA were synthesized using Oleksyszyn oxidation reaction, and their inhibitory activities on cleaving fibronectin (both human and bovine) and IGFBPs were investigated. To elucidate the role of PSA in the development and progression of prostate cancer, the regulation of the PSA activity on these two physiological substrates was clearly illustrated by modulating the concentrations of inhibitors, i.e. cleavages of both fibronectin and IGFBPs by PSA are inhibited by structure specific designed diphenyl phosphonate esters, consistent with the putative degradation. The inhibition data of two synthetic phosphonate ester derivatives, as lead compounds, will facilitate the development of more specific inhibitors of PSA activity, likely to modulate the physiological control of the IGF in human prostatic cell growth.

Requirement for G proteins in insulin-like growth factor-I-induced growth of prostate cells.

Elevated levels of IGF-I in the circulation are associated with increased risk for the development of prostate cancer in men, and transgenic expression of human IGF-I in mouse epithelial prostate cells results in spontaneous prostate tumorigenesis. Little, however, is known about the mechanisms involved in the IGF-I-regulated growth of prostate cells. Here, we have demonstrated that treatment with IGF-I induces the activation of the mitogenic extracellular signal-regulated kinase (ERK) pathway and the growth of human prostate cells. Stimulation with IGF-I also promoted the tyrosine phosphorylation of epidermal growth factor receptor (EGFR). Signal relay from IGF-I to ERK requires heterotrimeric G proteins and EGFR; inhibition of Gi/o protein activation by pertussis toxin, or EGFR by tyrphostin AG1478 obliterated the ability of IGF-I to promote ERK activation. Further, treatment with pertussis toxin inhibited the IGF-I-mediated prostate cell growth. These data demonstrated the requirement of heterotrimeric G proteins in IGF-I-regulated prostate cell growth and suggest the potential utility of the G proteins as effective drug targets to combat this common cancer.

Lycopene Inhibits the Growth of Normal Human Prostate Epithelial Cells in Vitro

Lycopene has repeatedly been shown to inhibit the growth of human prostate cells in vitro. However, previous studies with lycopene have focused on cancer specimens, and it is still unclear whether this carotenoid affects the growth of normal human prostate cells as well. Therefore, we investigated the effects of lycopene on normal human prostate epithelial cells (PrEC) by treating them with synthetic all-E-lycopene (up to 5 micromol/L) and assessing proliferation via [3H]thymidine incorporation. The effects of lycopene on cell cycle progression were investigated via flow cytometry. To elucidate whether lycopene modulates cyclins involved in cell cycle progression, protein expressions of cyclins D1 and E were analyzed. The results show that lycopene significantly inhibited the growth of PrEC in a dose-dependent fashion. Flow cytometry revealed a significant cell cycle arrest in the G0/G1 phase. This effect was confirmed by inhibition of cyclin D1 protein expression, whereas cyclin E levels remained unchanged. The results demonstrate that lycopene inhibits growth of nonneoplastic PrEC in vitro. We hypothesize that lycopene might likewise inhibit the growth of prostatic epithelial cells in vivo. This might have an effect on prostate development and/or on enlargement of prostate tissue as found in benign prostate hyperplasia, a potential precursor of prostate cancer.

Detection of a cell-cycle inhibitor of Petunia hybrida protoplasts in an Arthrospira platensis extract

A chloroform crude extract of whole Arthrospira platensis cells, provisionally named A. platensis auto-inhibitor (APAI), was inhibitory to growth of human prostatic cells and was toxic to them at less than 25 μg/ml. With cultured protoplasts of Petunia hybrida, APAI was growth inhibitory, without cytotoxicity, at 500 μg/ml. Using flow cytometry, it was seen that APAI induced arrest of the plant cell division cycle at the G1 phase. © Rapid Science Ltd. 1998

Effect of spermatocele fluid on growth of human prostatic cells in culture.

The present study was carried out to investigate whether testicular fluid derived from a spermatocele contains substance(s) that promote the growth of human prostatic cells in culture. Human spermatocele fluid was centrifuged to sediment spermatozoa. The supernatant was then added to cultures of human prostatic stromal or epithelial cells that were isolated from surgical specimens of benign prostatic hyperplasia. Addition of spermatocele fluid in quantities of 1 microgram/ml of protein resulted in a significant increase in the number of both prostatic stromal and epithelial cells at the end of a 6-day culture period. Human serum at equivalent protein concentrations in the culture medium had no stimulatory effect. At least two separate growth-promoting factors were found in spermatocele fluid, one for stromal cells and one for epithelial cells. The mitogen for stromal cells was heat labile and persisted after treatment with activated charcoal. The factor for epithelial cells was heat stable but was removed by charcoal treatment. These observations are consistent with the concept that the human testis secretes nonandrogenic substances that can promote prostatic growth.