Zinc chelation: a metallothionein 2A's mechanism of action involved in osteosarcoma cell death and chemotherapy resistance

Title	Zinc chelation: a metallothionein 2A's mechanism of action involved in osteosarcoma cell death and chemotherapy resistance
Authors	N Habel, Z Hamidouche, I Girault, A Patiño-García, F Lecanda, P J Marie, O Fromigué
Magazine	Cell Death & Disease
Date	10/24/2013
DOI	10.1038/cddis.2013.405
Introduction	Osteosarcoma is the most prevalent bone tumour in children and adolescents. Chemotherapy response is crucial for patient survival. Prior studies indicated that statins have antitumour properties, such as inducing apoptosis, reducing cell migration, and enhancing drug cytotoxicity. Transcriptomic comparisons showed that metallothionein 2A (MT2A) is significantly expressed in statin-treated cells. MT2A overexpression decreases zinc levels, reducing osteosarcoma cell viability and promoting differentiation. Conversely, MT2A silencing inhibits osteoblastic markers without affecting viability. MT2A overexpression induces chemoresistance by chelating platinum drugs and altering p53 zinc-dependent activity. In contrast, MT2A abrogation enhances drug efficacy in osteosarcoma cells. Clinical samples show low MT2A levels correlate with better prognosis, while high levels indicate poor prognosis. Overall, MT2A contributes to chemotherapy resistance in osteosarcoma, partly through zinc chelation, and may serve as a prognostic marker for chemotherapy sensitivity.
Quote	N Habel, Z Hamidouche and I Girault et al. Zinc chelation: a metallothionein 2A's mechanism of action involved in osteosarcoma cell death and chemotherapy resistance. Cell Death Dis. 2013. Vol. 4(10):e874-. DOI: 10.1038/cddis.2013.405
Element	Zinc (Zn) , Platinum (Pt)
Topics	Biomedical Materials
Industry	Pharmaceutical Industry