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2‐Chloroadenosine modulates PAR‐1 and IL‐23 expression and enhances docetaxel effects on PC3 cells
Author(s) -
Minelli Alba,
Bellezza Ilaria,
Tucci Arianna,
Conte Carmela,
Bracarda Sergio,
Culig Zoran
Publication year - 2008
Publication title -
the prostate
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.295
H-Index - 123
eISSN - 1097-0045
pISSN - 0270-4137
DOI - 10.1002/pros.20703
Subject(s) - docetaxel , lncap , prostate cancer , cancer research , medicine , apoptosis , cell cycle , immune system , cancer , endocrinology , biology , immunology , biochemistry
BACKGROUND Docetaxel‐based chemotherapy is the only treatment that demonstrated an overall survival benefit in men with hormone refractory prostate cancer. 2‐CADO inhibits the growth of PC3 cells by inducing apoptosis and cell cycle arrest through a mechanism that involves cellular uptake. METHODS Androgen‐independent and ‐sensitive (PC3 and LNCaP) prostate cancer cells and non‐neoplastic HECV cells were used in the study. Proliferation and cell cycle progression were analyzed in the presence of 2‐CADO and Docetaxel. Invasive potential was assessed by soft agar assay and metastatic ability by adhesion assay. IL‐23 and PAR‐1 expression were determined by real time PCR. RESULTS 2‐CADO pre‐treatment followed by Docetaxel at subclinical dosage reduced the viability of either PC3 or LNCaP while it did not enhance Docetaxel‐induced cytotoxicity in adherent non‐neoplastic HECV. The drugs reduced the invasive potential of PC3 cells by inducing apoptosis and blocking cell cycle progression in the S‐phase. Down‐regulation of PAR‐1 gene expression resulted in a slightly lower metastatic potential, whereas up‐regulation of IL‐23 induced the activation of the immune system. CONCLUSIONS Pretreatment of PC3 cells with 2‐CADO decreased the effective concentration of Docetaxel, lowered the metastatic potential, and induced the production of cytokines known to stimulate the immune response against cancer. The treatment was effective for prostate cancer cells independently on their androgen sensitiveness. Prostate 68: 360–372, 2008. © 2008 Wiley‐Liss, Inc.