Effect of quinolinyl acrylate derivatives on prostate cancer in vitro and in vivo

Abstract

Quinolines and acrylates are chemical compounds which were previously described as potential antitumor agents. In this study, a series of seven new quinolinyl acrylate derivatives were synthesized and evaluated against human prostate cancer cells PC-3 and LNCaP in vitro and in vivo. The most effective compound (E)-methyl 2-(7-chloroquinolin-4-ylthio)-3-(4 hydroxyphenyl) acrylate reduced the viability in both cell lines in a time- and dose-dependent manner. Inhibitory effects were also observed on the adhesion, migration, and invasion of the prostate cancer cells as well as on the neoangiogenesis, clonogenic and MMP-9 activity. The effect in vivo was studied in PC-3 xenografts in nude mice. The results were concordant with the in vitro effects and showed decreased tumor growth in treated animals compared to controls. The study suggests the multi-target efficacy of the quinolinyl derivate against human prostate cancer cells and supports its potential therapeutic usefulness.

Potential antitumour and pro-oxidative effects of (E)-methyl 2-(7-chloroquinolin-4-ylthio)-3-(4-hydroxyphenyl) acrylate (QNACR)

“…In addition, it has been demonstrated that epigallocatechin gallate (EGCG) induces ROS leading to DNA oxidative damage, which could be responsible for its antitumour actions 6 . QNACR could also inhibits angiogenesis, as we already reported recently in another study 7 and this effect could be due to its pro-oxidative properties besides its actions inhibiting MMP9; indeed neovascularization suppression in vivo and in vitro could be a response of augmenting ROS generation 20 . The involvement of QNACR on angiogenesis inhibition and apoptosis should be addressed in further studies to understand the more specific molecular mechanism of this analogue.…”

“…The adaptive response that followed this acute oxidative injury was not sufficient to spare MCF-7 cells from the toxic effects of QNACR. These results suggest that besides its effects on the inhibition of matrix metalloproteases and its ability to decrease tumour growth in animal models 7 , the antitumour activity of this compound could be also involved in the disturbance of the oxidant/antioxidant status. …”

“…It has been recently reported the potential antitumour properties of different quinoline acrylate derivatives 7 , and especial attention has been paid to (E)-Methyl 2-(7-chloroquinolin-4-ylthio)-3-(4-hydroxyphenyl) acrylate (QNACR), due to its ability to inhibit cell adhesion, migration, invasion, angiogenesis matrix metalloproteases in vitro and tumour growth in vivo 7 . Thus, in the present study we addressed the cytotoxic and pro-oxidative effects of QNACR in breast cancer cells.…”

“…The synthesis and physicochemical evaluations of QNACR ( Figure 1) were performed according to a previous procedure 7 . Briefly, the melting point was determined on a Thomas micro hot stage apparatus and infrared spectra as KBr pellets on a Shimadzu model 470 spectrophotometer.…”

“…The dose-dependent effects of each compound on cell viability were assessed using the Alamar Blue test (Invitrogen ® ) according to 7 and the IC 50 values obtained were defined as the concentration of tested compounds resulting in a 50% reduction of the cell viability compared to vehicle-treated cells. Further evaluations of QNACR were performed using its IC 50 value.…”