Associação Portuguesa de Investigação em Cancro
Manganese complexes as an alternative to platinum in cancer therapy
Manganese complexes as an alternative to platinum in cancer therapy
Authors and Affiliations:
Oscar A. Lenis-Rojas1, Beatriz Carvalho2,3, Rui Cabral2,3, Margarida Silva2,3,4, Sofia Friães1, Catarina Roma-Rodrigues2,3, Marta S. H. Meireles1, Clara S. B. Gomes5,6, Jhonathan A. A. Fernández7, Sabela F. Vila8, Juan A. Rubiolo8, Laura Sanchez8,9, Pedro V. Baptista2,3, Alexandra R. Fernandes2,3, Beatriz Royo1
1Instituto de Tecnologia Química e Biológica António Xavier, ITQB, Av. da República, 2780-157 Oeiras, Portugal.
2UCIBIO, Departamento Ciências da Vida, NOVA School of Science and Technology, Campus de Caparica, 2829-516 Caparica, Portugal.
3Associate Laboratory i4HB - Institute for Health and Bioeconomy, NOVA School of Science and Technology, NOVA University Lisbon, 2819-516 Caparica, Portugal
4Imed. Faculdade de Farmácia, Universidade de Lisboa, Av. Prof. Gama Pinto, 1649-003 Lisboa, Portugal
5LAQV-REQUIMTE, Departamento de Química, NOVA School of Science and Technology, 2829-516, Caparica, Portugal.
6Departamento de Química, NOVA School of Science and Technology, UCIBIO, 2829-516 Caparica, Portugal
7Laboratory of Zebrafish, Department of Medical Genetics and Genomic Medicine School of Medical Sciences, University of Campinas (UNICAMP), Campinas, 13083-887, São Paulo, Brazil.
8Departamento de Zoología Genética y Antropología Física, Facultad de Veterinaria, Universidad de Santiago de Compostela, Campus de Lugo, 27002 Lugo, Spain.
9Preclinical Animal Models Group. Health Research Institute of Santiago de Compostela (IDIS), 15706 Santiago de Compostela, A Coruña, Spain.
Abstract:
The antiproliferative activity of [Mn(CO)3(N^N)Br] (N^N = phendione 1, bipy 3) and of the two newly synthesized Mn complexes [Mn(CO)3(acridine)(phendione)]OTf (2) and [Mn(CO)3(di-triazole)Br] (4) has been evaluated by MTS against three tumor cell lines A2780 (ovarian carcinoma), HCT116 (colorectal carcinoma), HCT116doxR (colorectal carcinoma resistant to doxorubicin), and in human dermal fibroblasts. The antiproliferative assay showed a dose-dependent effect higher in complex 1 and 2 with a selectivity toward ovarian carcinoma cell line 21 times higher than in human fibroblasts. Exposure of A2780 cells to IC50 concentrations of complex 1 and 2 led to an increase of reactive oxygen species that led to the activation of cell death mechanisms, namely via intrinsic apoptosis for 2 and autophagy and extrinsic apoptosis for 1. Both complexes do not target DNA or interfere with cell cycle progression but are able to potentiate cell migration and neovascularization (for 2) an indicative that their application might be directed for initial tumor stages to avoid tumor invasion and metastization and opening a new avenue for complex 2 application in regenerative medicine. Interestingly, both complexes do not show toxicity in both in vivo models (CAM and zebrafish).
Journal: Journal of Biological Inorganic Chemistry (JBIC)
Link: https://link.springer.com/article/10.1007/s00775-021-01910-7