B1 but not B2 bradykinin receptor agonists promote DU145 prostate cancer cell proliferation and migration

• Published in: African health sciences Vol. 14; no. 3; pp. 657 - 662
• Main Authors: Naidu, N, Botha, J H, Naidoo, S
• Format: Journal Article
• Language: English
• Published: Uganda Makerere Medical School 01.01.2014
• Subjects: Bradykinin B1 Receptor Antagonists; Bradykinin B2 Receptor Antagonists; Cancer; Cell Line; Cell Movement - drug effects; Cell Proliferation - drug effects; Endothelium, Vascular - cytology; Endothelium, Vascular - drug effects; Endothelium, Vascular - metabolism; Health and Medicine; Humans; Male; Medical research; Medical treatment; Prostatic Neoplasms - pathology; Receptors, Bradykinin; Endothelial; Kallikrein; Angiogenesis; Prostate tumour; Conditioned medium; Bradykinin receptor antagonists
• ISSN: 1680-6905; 1729-0503; 1680-6905
• DOI: 10.4314/ahs.v14i3.22

The kallikrein-kinin system (KKS) is an endogenous pathway involved in angiogenesis and tumourigenesis, both vital for cancer growth and progression. To investigate the effect of two bradykinin receptor (B1R and B2R) agonists on growth and motility of prostate tumour (DU145) and micro-vascular endothelial cells (dMVECs). Increasing concentrations of selective B1R and B2R agonists were added to cultured cells. Cell proliferation and migration were assessed using the 3-[4,5 dimethylthiazol-2-yl]-2,5-diphenyl-tetrazolium bromide (MTT) and modified Boyden Chamber assays, respectively. Where significant stimulation was found, the influence of an antagonist was also investigated. Neither growth nor motility of endothelial cells was affected by either agonist. In DU145 cells, while the B2R agonist was without any significant effect, the B1R agonist stimulated proliferation and migration at concentrations of 10nM and 50nM respectively. Further, this effect was abrogated when cells were pre-incubated with a B1R antagonist. Unlike the physiologically-active B2R, the pathologically-inducible B1R may be implicated in prostate tumourigenic events. The involvement of the KKS in malignant prostate pathology supports on-going exploration of bradykinin receptor antagonists as target candidates in the development of alternate approaches to cancer therapy.