[Ru(pipe)(dppb)(bipy)]PF6: A novel ruthenium complex that effectively inhibits ERK activation and cyclin D1 expression in A549 cells

Abstract

Lung cancer is the most frequent type of cancer worldwide. In Brazil, only 14% of the patients diagnosed with lung cancer survived 5years in the last decades. Although improvements in the therapeutic approach, it is relevant to identify new chemotherapeutic agents. In this framework, ruthenium metal compounds emerge as a promising alternative to platinum-based compounds once they displayed lower cytotoxicity and more selectivity for tumor cells. The present study aimed to evaluate the antitumor potential of innovative ruthenium(II) complex, [Ru(pipe)(dppb)(bipy)]PF (PIPE) on A549 cells, which is derived from non-small cell lung cancer. Results demonstrated that PIPE effectively reduced the viability and proliferation rate of A549 cells. When PIPE was used at 9μM there was increase in G0/G1 cell population with concomitant reduction in frequency of cells in S-phase, indicating cell cycle arrest in G1/S transition. Antiproliferative activity of PIPE was associated to its ability of reducing cyclin D1 expression and ERK phosphorylation levels. Cytotoxic activity of PIPE on A549 cells was observed when PIPE was used at 18μM, which was associated to its ability of inducing apoptosis by intrinsic pathway. Taken together, the data demonstrated that PIPE is a promising antitumor agent and further in vivo studies should be performed.

Calein C, a Sesquiterpene Lactone Isolated From Calea Pinnatifida (Asteraceae), Inhibits Mitotic Progression and Induces Apoptosis in MCF-7 Cells

“…Cell cycle analysis was performed according to Ferreira-Silva et al ( 2017 ). Briefly, cells were treated with calein C for 24 h at 7.5 and 15.0 μg mL −1 .…”

Ruthenium Complexes as Promising Candidates against Lung Cancer

“…Similar results were also obtained for the arene Ru(II) carbazole-based hydrazone complexes Ru51-53 [(η 6 -benzene) Ru(L) Cl] (L = carbazolone benzhydrazone ligands) [64] (Figure 9), whereas Ru30 [54] and Ru48-49 [62] induced apoptosis and cell cycle arrest of A549 lung cancer cells in the G2/M phase. The cytotoxicity of {[Ru(pipe)(dppb)(bipy)]PF 6 } (pipe = piperonylic acid, dppb = 1,4-bis(diphenylphosphino) butane) (Ru50) on A549 cells has been associated with the induction of cell apoptosis via the intrinsic pathway [63]. The number of cells was significantly increased in the G0/G1 phase of the cell cycle, while the population of A549 cells in the S-phase was reduced when 9 µM of Ru50 was used.…”

“…The cytotoxicity of {[Ru(pipe)(dppb)(bipy)]PF 6 } (pipe = piperonylic acid, dppb = 1,4-bis(diphenylphosphino) butane) ( Ru50 ) on A549 cells has been associated with the induction of cell apoptosis via the intrinsic pathway [ 63 ]. The number of cells was significantly increased in the G0/G1 phase of the cell cycle, while the population of A549 cells in the S-phase was reduced when 9 μM of Ru50 was used.…”

“…The number of cells was significantly increased in the G0/G1 phase of the cell cycle, while the population of A549 cells in the S-phase was reduced when 9 μM of Ru50 was used. These results indicated that the G1/S transition depended on the antineoplastic ability of Ru50 , which reduced the cyclin D1 expression levels and attenuated ERK phosphorylation [ 63 ]. Furthermore, Ru(II)-based compounds, such as the polypyridyl Ru complex Ru47 [ 61 ], arrested cell growth in the S-phase.…”

Piperine–Chlorogenic Acid Hybrid Inhibits the Proliferation of the SK-MEL-147 Melanoma Cells by Modulating Mitotic Kinases

“…Cell cycle analysis was performed according to Ferreira-Silva et al [ 71 ]. Briefly, SK-MEL-147 cells were seeded into 35 mm Petri plates at a density of 1 × 10 5 cells/plate.…”