Vasoactive intestinal peptide induces cyclooxygenase-2 expression through nuclear factor-kappaB in human prostate cell lines Differential time-dependent responses in cancer progression.
The effect of vasoactive intestinal peptide (VIP) on cyclooxygenase-2 (COX-2) expression was analyzed in human prostate non-neoplastic (RWPE-1) as well as cancer androgen-dependent (LNCaP) and independent (PC3) cells. The three cell lines expressed VIP mRNA and VIP peptide, as measured by RT-PCR and immunochemistry, which supports an autocrine/paracrine action of VIP in the prostate gland. VIP levels were progressively higher from non-neoplastic to androgen-dependent and independent cells. Real-time RT-PCR and Western-blotting showed that VIP stimulated both COX-2 mRNA and protein expression in a faster manner as prostate cancer stage progressed (i.e. RWPE1<LNCaP<PC3 cells). Furthermore, VIP induced higher levels of COX-2 protein expression in cancer cells as compared with non-neoplastic cells. The anti-inflammatory agent curcumin blocked VIP-induced COX-2 expression in all cell lines studied supporting the involvement of nuclear factor-kappaB (NFkappaB) in such a response. In fact, VIP increased the translocation of the NFkappaB p50 subunit to the nucleus and the binding of the active form to its target gene promoter, as measured by Western-blotting and ELISA, respectively. VIP provoked faster responses according to the most aggressive status in cancer progression (androgen-independent situation). These results together with the existence of two NFkappaB sites in the COX-2 gene promoter together suggest that COX-2 may be a target for VIP in prostate cancer progression. On the other hand, VIP could be a proinflammatory cytokine acting through the NFkappaB/COX-2 system.
Fernández-Martínez
Ana B
AB
Department of Biochemistry and Molecular Biology, University of Alcalá, 28871 Alcalá de Henares, Spain.
Collado
Beatriz
B
Bajo
Ana M
AM
Sánchez-Chapado
Manuel
M
Prieto
Juan C
JC
Carmena
María J
MJ
D045744:Cell Line, Tumor; D003474:Curcumin / Q000494:pharmacology; D051546:Cyclooxygenase 2 / Q000235:genetics* / Q000378:metabolism*; D018450:Disease Progression; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D006801:Humans; D008297:Male; D008565:Membrane Proteins / Q000235:genetics* / Q000378:metabolism*; D016328:NF-kappa B / Q000378:metabolism*; D011471:Prostatic Neoplasms / Q000235:genetics / Q000473:pathology*; D021381:Protein Transport / Q000187:drug effects; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D013997:Time Factors; D014660:Vasoactive Intestinal Peptide / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology*
D008565:Membrane Proteins; D016328:NF-kappa B; D012333:RNA, Messenger; D014660:Vasoactive Intestinal Peptide; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D003474:Curcumin