Effect of tamoxifen and retinoic acid on bradykinin induced proliferation in MCF‐7 cells

Abstract

Chemopreventive approaches for the treatment of breast cancer have been validated clinically and with in vitro studies. The combined action of tamoxifen/all-trans retinoic acid was advantageous in MCF-7 cells, reducing cell proliferation, Bcl-2 and c-Myc protein levels and increasing E-Cadherin protein levels and Gap junctional Intercellular Communication. We further investigated their combined effect in the presence of bradykinin, a pro-inflammatory agent, previously reported to contribute to the proliferation of breast cancer cells. Bradykinin increased MCF-7 cell proliferation, c-Myc levels and ERK1/2 activity. The co-incubation of bradykinin-MCF-7 cells with tamoxifen/all-trans retinoic acid reduced cell proliferation, ERK1/2 activity, as well as Bcl-2, c-Myc, and bradykinin receptor-2 levels, without altering the enhanced E-cadherin levels induced by tamoxifen/all-trans retinoic acid. We showed that the anti-tumoral effect of tamoxifen/all-trans retinoic acid is beneficial in MCF-7 breast cancer cells grown in a bradykinin-pro-mitogenic environment, an effect that might be, at least in part, through the MAPK pathway and B2-bradykinin receptor inhibition.

Bradykinin stimulates IL-6 production and cell invasion in colorectal cancer cells

“…As the most prominent member of the kinin group, bradykinin (BK) is an important player in the regulation of inflammation and cancer (13,14). Accumulating research shows that BK treatment can induce the activation of multiple intracellular pathways such as MAPK and PI3K/AKT signaling pathways in cancer cells (5,15), and thus contributes to the proliferation, angiogenesis and migration of cancer cells (16)(17)(18). Our present study demonstrated for the first time that BK treatment activated B2R and ERK1/2, which then led to an increase in IL-6 production, which finally promoted cell invasion and migration of colorectal cancer cells.…”

Imaging Bradykinin B1 Receptor with 68Ga-Labeled [des-Arg10]Kallidin Derivatives: Effect of the Linker on Biodistribution and Tumor Uptake

“…[4][5][6][7][8][9][10][11][12][13] The activation of B1R was reported to induce angiogenesis and enhance survival, proliferation and migration/metastasis of cancer cells. [14][15][16][17][18][19][20][21][22] Consequently, B1R has been proposed as a promising therapeutic target of cancer. 23 The use of non-invasive modalities such as positron emission tomography (PET) for imaging B1R expression could potentially facilitate the development of B1R-targeted therapies.…”

Exploiting cancer’s phenotypic guise against itself: targeting ectopically expressed peptide G-protein coupled receptors for lung cancer therapy

“…Cancer cells produce and secrete the neuropeptides CCK/gastrin [ 34 , 129 ], GRP and NMB [ 130 , 131 ], bradykinin [ 132 ], and vasopressin [ 133 , 134 ]. A plethora of evidence exists elucidating the autocrine growth and pro-proliferative effects exerted by CCK/gastrin [ 135 , 136 ], GRP and NMB [ 137 , 138 ], bradykinin [ 139 , 140 ] and vasopressin [ 21 , 94 , 95 , 141 , 142 ] through their respective receptors. In the process, they increase the colony number of cancer cells, including lung cancer [ 21 , 135 , 143 ].…”

“…Other BRS-3 agonists such as (DTyr 6 , R-Apa 11 , Phe 13 , Nle 14 )bombesin 6–14 (BA2) and (DTyr 6 , R-Apa 11 , 4-Cl,Phe 13 , Nle 14 )bombesin 6–14 (BA3) also caused EGFR transactivation in NCI-H1299-BRS-3 cells [ 146 ]. Furthermore, it has been found that CCK/ gastrin [ 135 , 147 – 150 ], GRP [ 53 , 54 , 131 , 138 , 151 , 152 ], bradykinin [ 153 , 154 ] and vasopressin [ 21 , 155 , 156 ] bind with high affinity to their cognate receptors to promote DNA synthesis [ 157 ], increase intracellular calcium levels [ 37 , 132 , 143 , 147 – 150 , 153 – 155 , 158 ], promote cellular growth, proliferation, survival [ 139 , 140 , 159 – 165 ], cause loss of cell adhesion, and stimulate tumor progression, invasion, migration and metastasis [ 166 – 169 ]. Moreover, it is thought that CCK/gastrin [ 170 ], GRP and NMB [ 130 , 131 , 171 ], and bradykinin [ 172 , 173 ], by acting on their cognate receptors, promote angiogenesis and suppress apoptosis.…”