VIP and PACAP are autocrine factors that protect the androgen‐independent prostate cancer cell line PC‐3 from apoptosis induced by serum withdrawal

• Published in: British journal of pharmacology Vol. 139; no. 5; pp. 1050 - 1058
• Main Authors: Gutiérrez‐Cañas, Irene, Rodríguez‐Henche, Nieves, Bolaños, Oscar, Carmena, María J, Prieto, Juan C, Juarranz, María G
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Publishing Ltd 01.07.2003; Nature Publishing
• Subjects: Androgens - genetics; Androgens - physiology; apoptosis; Apoptosis - drug effects; Apoptosis - physiology; Autocrine Communication - drug effects; Autocrine Communication - physiology; Biological and medical sciences; Cell Line, Tumor - drug effects; Cell Line, Tumor - metabolism; Cell Survival - drug effects; Cell Survival - physiology; Culture Media, Serum-Free - pharmacology; Dose-Response Relationship, Drug; Humans; Male; Medical sciences; Neuropeptides - antagonists & inhibitors; Neuropeptides - genetics; Neuropeptides - physiology; PACAP; PC‐3; Pituitary Adenylate Cyclase-Activating Polypeptide; prostate cancer; Prostatic Neoplasms - genetics; Prostatic Neoplasms - metabolism; Vasoactive Intestinal Peptide - antagonists & inhibitors; Vasoactive Intestinal Peptide - pharmacology; VIP; apoptosis; prostate cancer; PACAP; PC-3; VIP
• ISSN: 0007-1188; 1476-5381
• DOI: 10.1038/sj.bjp.0705317

In the present study, we describe the expression of the neuropeptides vasoactive intestinal peptide (VIP) and pituitary adenylate cyclase‐activating polypeptide (PACAP) as well as their receptors in PC‐3 cells, a human prostate cancer cell line. In addition, we have investigated their role in apoptosis induced by serum starvation. By RT–PCR and immunocytochemistry assays, we have demonstrated the production of VIP and PACAP in PC‐3 cells. We have demonstrated by RT–PCR and binding assays the expression of common PACAP/VIP (VPAC1 and VPAC2) receptors, but not PACAP‐specific (PAC1) receptors. The pharmacological profile of [125I]‐VIP binding assays was as follows: VPAC1 antagonist=VPAC1 agonist>VIP>VPAC2 agonist (IC50=1.2, 1.5, 2.3 and 30 nM, respectively). In addition, both receptor subtypes are functional since VIP, PACAP‐27 or VPAC1 and VPAC2 agonists all increased the intracellular levels of cAMP. The expression of both peptides and their receptors is similar in serum‐cultured and serum‐deprived PC‐3 cells. The treatment of serum‐deprived PC‐3 cells with exogenous VIP or PACAP‐27 increases cell number and viability in a dose‐dependent manner, as demonstrated by cellular counting and MTT assays. The increased cell survival is exerted through the VPAC1 receptor, since a VPAC1, but not VPAC2, receptor agonist, mimics the effects and a VPAC1 receptor antagonist blocks it. Moreover, VIP and PACAP‐27 inhibit genomic DNA fragmentation in PC‐3 cells triggered by serum starvation, and increase the immunoreactivity of the antiapoptotic protein bcl‐2. Our results suggest that VIP and PACAP are autocrine/paracrine factors that protect PC‐3 cells from apoptosis through VPAC1 receptors. British Journal of Pharmacology (2003) 139, 1050–1058. doi:10.1038/sj.bjp.0705317