Effects of Antiproliferative Protein (APP) on Modulation of Cytosolic Protein Phosphorylation of Prostatic Carcinoma Cell Line LNCaP

Antiproliferative protein (APP) isolated from conditioned media of two androgen-independent prostatic carcinoma cell lines, PC3 and Du-145 was shown to inhibit selectively cell proliferation of androgen-dependent prostate cancer cell line LNCaP in a dose dependent manner. This protein was further purified with HPLC using hydrophobic interaction column (phenyl 5PW) and was used to study the modulation of protein phosphorylation of LNCaP cells. The data indicated that antiprolif- erative protein could partially change the cytosolic protein phosphorylation. When compared with control LNCaP cells, in APP-treated cells 4 new proteins (88, 46, 30 and 18 kDa) were phosphorylated, while a 72 kDa phosphoprotein was de-phosphorylated. The same results were obtained when two types of protein kinase activators were used. Protein kinase activators showed that the above changes of protein phosphorylation are not due to the protein kinase C or DNA protein kinase activity. These data may indicate the inhibition of LNCaP cell's proliferation by APP may be is due to the modulation of protein kinases and as a result due to interference on second messenger pathway.