Advanced search
Start date
Betweenand
Related content
(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

Three-dimensional cell culture models for metallodrug testing: induction of apoptosis and phenotypic reversion of breast cancer cells by the trans-[Ru(PPh3)(2)(N,N-dimethyl-N-thiophenyl-thioureato-k(2)O,S)(bipy) ]PF6 complex

Full text
Author(s):
Becceneri, Amanda B. [1] ; Fuzer, Angelina M. [1] ; Plutin, Ana M. [2] ; Batista, Alzir A. [3] ; Lelievre, Sophie A. [4, 5] ; Cominetti, Marcia R. [1]
Total Authors: 6
Affiliation:
[1] Univ Fed Sao Carlos, Dept Gerontol, Rod Washington Luis, Km 235, BR-13565905 Sao Carlos - Brazil
[2] Univ La Habana, Fac Quim, Zapata S-N Entre G & Carlitos, Havana 10400 - Cuba
[3] Univ Fed Sao Carlos, Dept Chem, Rod Washington Luis, Km 235, BR-13565905 Sao Carlos, SP - Brazil
[4] Purdue Univ, Dept Basic Med Sci, 625 Harrison St, W Lafayette, IN 47907 - USA
[5] Purdue Univ, Ctr Canc Res, 625 Harrison St, W Lafayette, IN 47907 - USA
Total Affiliations: 5
Document type: Journal article
Source: INORGANIC CHEMISTRY FRONTIERS; v. 7, n. 16, p. 2909-2919, AUG 21 2020.
Web of Science Citations: 4
Abstract

Many studies have revealed the advantages of using three-dimensional (3D) culture over traditional twodimensional (2D) monolayer techniques. The 3D cell culture models represent biologically relevant approaches to better mimic the tumor organization observed in vivo. These models have high potential for anticancer drug development and screening, for which challenges include tumor cell resistance to treatment and the risk of toxicity for patients. Many anticancer drug candidates do not reach clinical trials as they fail preclinical tests in vivo, although they were promising in 2D cultures. Models from 3D cell cultures are proposed as intermediate screening filters between 2D and in vivo assays. It has been suggested that ruthenium complexes have great potential for breast cancer treatment. Here, we tested the trans{[}Ru(PPh3)(2)(N,N-dimethyl-N-thiophenylthioureato-k(2)O,S)(bipy)]P F6 complex in breast cancer cell lines using different 3D culture techniques, including the embedded, `on top' and disease-on-a-chip (DOC) models that reproduce physical aspects of the tumor microenvironment. The complex had pronounced but distinct cytotoxic effects on tumors cultured in collagen I of appropriate stiffness for the disease stage; the extent of induced apoptosis depends on the preinvasive (S2 cells) and invasive (T4-2 and MDA-MB-231 cells) nature of triple-negative breast cancer models. Remarkably, in the DOC model, which simulates breast ductal architecture, the complex was cytotoxic for T4-2 tumors but had no remarkable effect on the differentiated luminal epithelial S1 cells, demonstrating selectivity against cancer cells. In addition, a lower concentration of the complex abrogated the malignant phenotype of the T4-2 cells with reduction of EGFR, p50 NF kappa B, and beta 1-integrin expression. To the best of our knowledge, this work uniquely demonstrates the effects of a ruthenium complex on the induction of apoptosis and on the phenotypic reversion of tumor cells in 3D cultures. These results warrant moving to in vivo evaluation of this ruthenium complex. (AU)

FAPESP's process: 17/01287-2 - Screening of candidates to new antitumoral drugs by three-dimensional cell culture
Grantee:Angelina Maria Fuzer
Support Opportunities: Scholarships in Brazil - Post-Doctoral
FAPESP's process: 18/19342-2 - Metal complexes with dirivative ligands of lawsone and acylthioureas, with anticancer potential activities: study in vitro and in vivo.
Grantee:Alzir Azevedo Batista
Support Opportunities: Regular Research Grants
FAPESP's process: 13/07600-3 - CIBFar - Center for Innovation in Biodiversity and Drug Discovery
Grantee:Glaucius Oliva
Support Opportunities: Research Grants - Research, Innovation and Dissemination Centers - RIDC
FAPESP's process: 17/20055-5 - Effects of ruthenium complex trans[Ru(ThySMet)(PPh3)2(bipy)]PF6 on breast tumor cells in three-dimensional culture
Grantee:Amanda Blanque Becceneri
Support Opportunities: Scholarships abroad - Research Internship - Doctorate
FAPESP's process: 15/24940-8 - EFFECTIVENESS OF STRUCTURAL CHANGES IN [10]-GINGEROL MOLECULE IN COMBINATION WITH THE CHEMOTHERAPEUTIC DOXORUBICIN FOR THE TREATMENT OF BREAST CANCER: IN VITRO AND IN VIVO STUDIES. ABSTRACT
Grantee:Márcia Regina Cominetti
Support Opportunities: Regular Research Grants
FAPESP's process: 14/25121-8 - Antitumor activity and mutagenic potential of New Ruthenium Complexes
Grantee:Amanda Blanque Becceneri
Support Opportunities: Scholarships in Brazil - Doctorate