ANTIPROLIFERATIVE EFFECT OF A PROSTATIC CELL-DERIVED ACTIVITY ON THE HUMAN ANDROGEN-DEPENDENT PROSTATIC-CARCINOMA CELL-LINE LNCAP

We have identified a new antiproliferative activity from the conditioned medium of two androgen-independent prostatic cancer cell lines, PC3 and DU-145. This antiproliferative activity selectively inhibited cell proliferation of an androgen-dependent prostate cancer cell line LNCaP in a dose-dependent manner. No antiproliferative activity was observed against mouse fibroblast 3T3, normal human lymphocytes, human leukemic cells, including promyelocyte HL-60 or T cell HUT-78, or human adenocarcinoma cell lines, including prostatic cells JCA-1, ovary NIH:OVCAR3, cervix C-33A, or breast MDA-MB-231. Cell cycle analysis revealed that the antiproliferative activity did not induce apoptosis in LNCaP cells, but it prevented some G(1) LNCaP cells from entering into the S phase of the cell cycle. The antiproliferative activity was sensitive to high temperature (100 degrees C) and to proteinase digestion; however, it was resistant to 56 degrees C, pH 2.0, and reducing agent treatment, as well as to DNase and RNase digestion. The antiproliferative activity was partially purified by gel filtration, ion-exchange chromatography, and SDS-PAGE, with an apparent molecular weight of 50 kD. The antiproliferative activity was not affected by neutralizing antibody against TGF-beta(1,2,3), TNF-alpha, PDGF, EGF, IL-1, IL-2, IL-3, IL-4, or IL-6.