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 condition ed medium of two androgen-independent prostatic cancer cell lines, PC3 and DU-145. This antiproliferative activity selectively inhibited cel l proliferation of an androgen-dependent prostate cancer cell line LNC aP in a dose-dependent manner. No antiproliferative activity was obser ved against mouse fibroblast 3T3, normal human lymphocytes, human leuk emic cells, including promyelocyte HL-60 or T cell HUT-78, or human ad enocarcinoma cell lines, including prostatic cells JCA-1, ovary NIH:OV CAR3, 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 sensitiv e to high temperature (100 degrees C) and to proteinase digestion; how ever, it was resistant to 56 degrees C, pH 2.0, and reducing agent tre atment, as well as to DNase and RNase digestion. The antiproliferative activity was partially purified by gel filtration, ion-exchange chrom atography, and SDS-PAGE, with an apparent molecular weight of 50 kD. T he antiproliferative activity was not affected by neutralizing antibod y against TGF-beta(1,2,3), TNF-alpha, PDGF, EGF, IL-1, IL-2, IL-3, IL- 4, or IL-6.