Proteomics

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Unlocking Selective Anticancer Mechanisms: Dinuclear Manganese Superoxide Dismutase Mimetics Combined with Pt(II) Complexes


ABSTRACT: We explored the in vitro activities of the dinuclear Mn2L2Ac and Mn2L2 complexes (where HL=2-{[di(2-pyridyl)- methylamino]-methyl}phenol), possessing dual superoxide dismutase(SOD) and catalase (CAT) activity, both individually and in conjunction with various Pt(II)-complexes, either as mixtures or as the Mn2-Pt adducts. Our findings revealed a notable up to 50% enhancement in the viability of healthy human breast cells, contrasted with a viability decrease as low as 50% in breast cancer cells upon combined treatments with Mn2 SOD mimics and Pt(II) complexes. Specifically, we synthesized and characterized the self-assembled Mn2-Pt adducts (isolated Mn2L2Pt and in situ Mn2L2Pt’), linking Mn2L2-core with the carboxylate group of PtDAPCl2 (dichloro(2,3-diaminopropionic acid) platinum(II)). The SOD activity of the isolated Mn2L2Pt adduct (kSOD=1.7×107 M-1 s-1) remained intact. We elucidated key mechanisms underlying the observed biological effects. We demonstrated that Mn2-containing formulations predominantly target mitochondrial processes, differently affecting the proteome of cancerous and healthy cells. They induced downregulation of H2S signaling and expression of mitochondrial complex I and III, as well as increased oxidative phosphorylation pathways and upregulation of EGFR in cancer cells. In contrast, healthy cells showed a decrease in EGFR expression and a moderate enrichment in oxidative phosphorylation pathways.

INSTRUMENT(S): Orbitrap Fusion Lumos

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Mammary Gland Epithelial Cell

DISEASE(S): Breast Cancer

SUBMITTER: Thibaut Vignane  

LAB HEAD: Milos Filipovic

PROVIDER: PXD051376 | Pride | 2024-08-28

REPOSITORIES: Pride

Dataset's files

Source:
Action DRS
Lumos13363_TV_MCF7_1_CON.raw Raw
Lumos13363_TV_MCF7_1_CON.raw.refined.mgf Mgf
Lumos13364_TV_MCF7_1_Mn2L2.raw Raw
Lumos13364_TV_MCF7_1_Mn2L2.raw.refined.mgf Mgf
Lumos13365_TV_MCF7_1_PtDAPCl2.raw Raw
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