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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

Ru(II)/diphenylphosphine/pyridine-6-thiolate complexes induce S-180 cell apoptosis through intrinsic mitochondrial pathway involving inhibition of Bcl-2 and p53/Bax activation

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Author(s):
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Pires, Wanessa Carvalho [1] ; Vieira Lima, Benedicto Augusto [2] ; Pereira, Flavia de Castro [1] ; Lima, Aliny Pereira [1] ; Mello-Andrade, Francyelli [1] ; Silva, Hugo Delleon [1] ; da Silva, Monize Martins [2] ; Colina-Vegas, Legna [2] ; Ellena, Javier [3] ; Batista, Alzir A. [2] ; Silveira-Lacerda, Elisangela de Paul [1]
Total Authors: 11
Affiliation:
[1] Univ Fed Goias, Inst Ciencias Biol, Lab Genet Mol & Citogenet, BR-74690900 Goiania, Go - Brazil
[2] Univ Fed Sao Carlos, Dept Quim, POB 676, BR-13565905 Sao Carlos, SP - Brazil
[3] Univ Sao Paulo, Inst Fis Sao Carlos, POB 369, BR-13560970 Sao Carlos, SP - Brazil
Total Affiliations: 3
Document type: Journal article
Source: Molecular and Cellular Biochemistry; v. 438, n. 1-2, p. 199-217, JAN 2018.
Web of Science Citations: 2
Abstract

The aim of this work was the synthesis, characterization, and cytotoxicity evaluation of three new Ru(II) complexes with a general formula {[}Ru(Spy)(bipy)(P-P)]PF6 {[}Spy = pyridine-6-thiolate; bipy = 2,2'-bipyridine; P-P = 1,2-bis(diphenylphosphine)ethane (1); 1,3-bis(diphenylphosphine) propane (2); and 1,1'-bis(diphenylphosphino)ferrocene] (4). Complex (3) with the 1,4-bis(diphenylphosphine)butane ligand, already known from the literature, was also synthesized, to be better studied here. The cytotoxicities of the complexes toward two kinds of cancerous cells (K562 and S-180 cells) were evaluated and compared to normal cells (L-929 and PBMC) by MTT assay. The complex {[}Ru(Spy)(bipy)(dppb)]PF6 (3) was selected to study both the cellular and molecular mechanisms underlying its promising anticancer action in S-180 cells. The results obtained from this study indicated that complex (3) induces cell cycle arrest in the G0/G1 phase in S-180 cells associated with a decrease in the number of cells in S phase. After 24 and 48 h of exposure to complex (3), the cell viability decreased when compared to the negative control. Complex (3) does not appear to be involved in the DNA damage, but induced changes in the mitochondrial membrane potential in S-180 cells. Furthermore, there was also an increase in the gene expression of Bax, Caspase 9, and Tp53. According to our results, complex (3) induces cell apoptosis through p53/Bax-dependent intrinsic pathway and suppresses the expression of active antiapoptotic Bcl-2 protein. (AU)

FAPESP's process: 14/10516-7 - Search for ruthenium (II) complexes, with chemotherapeutic properties: evaluation of possible sinergistic effects and possible action mechanism
Grantee:Alzir Azevedo Batista
Support Opportunities: Regular Research Grants