Metallothioneins (MTs) are small cysteine-rich intracellular proteins. The best-known biological functions of MTs are sequestration of metal ions and maintenance of redox homeostasis. Despite these protective functions, it has been demonstrated that MTs are involved in tumorigenesis, cellular differentiation, drug resistance, and metabolic disorders such as diabetes and obesity, in which MTs expression is substantially deregulated in adipose tissue. In addition, many studies have experimentally evidenced a possible role of MTs in the development of diabetes. Given the rich biochemical properties of MTs, it can be concluded that they are involved in several aspects of development and progression of obesity and diabetes. Thus, evaluation of expression of MTs could serve as biomarker to personalize available therapeutic interventions and possibly to develop novel advanced therapeutic modalities. Overall, the purpose of this review is analyze and review the latest studies aimed on the multiple roles of MTs in metabolic disorders, possible use of MTs as obesity and diabetes biomarkers and the role of MTs in cardioprotection during diabetes progression.

• Publication type
• Journal Article MeSH
• Review MeSH

Metallothionein-3 has poorly characterized functions in neuroblastoma. Cisplatin-based chemotherapy is a major regimen to treat neuroblastoma, but its clinical efficacy is limited by chemoresistance. We investigated the impact of human metallothionein-3 (hMT3) up-regulation in neuroblastoma cells and the mechanisms underlying the cisplatin-resistance. We confirmed the cisplatin-metallothionein complex formation using mass spectrometry. Overexpression of hMT3 decreased the sensitivity of neuroblastoma UKF-NB-4 cells to cisplatin. We report, for the first time, cisplatin-sensitive human UKF-NB-4 cells remodelled into cisplatin-resistant cells via high and constitutive hMT3 expression in an in vivo model using chick chorioallantoic membrane assay. Comparative proteomic analysis demonstrated that several biological pathways related to apoptosis, transport, proteasome, and cellular stress were involved in cisplatin-resistance in hMT3 overexpressing UKF-NB-4 cells. Overall, our data confirmed that up-regulation of hMT3 positively correlated with increased cisplatin-chemoresistance in neuroblastoma, and a high level of hMT3 could be one of the causes of frequent tumour relapses.

• MeSH
• Drug Resistance, Neoplasm drug effects   genetics   MeSH
• Cisplatin pharmacology   MeSH
• Chick Embryo MeSH
• Humans MeSH
• Metallothionein 3 biosynthesis   genetics   MeSH
• Cell Line, Tumor MeSH
• Neoplasm Proteins biosynthesis   genetics   MeSH
• Gene Expression Regulation, Neoplastic drug effects   MeSH
• Animals MeSH
• Check Tag
• Chick Embryo MeSH
• Humans MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Names of Substances
• Cisplatin MeSH
• Metallothionein 3 MeSH
• Neoplasm Proteins MeSH

Doxorubicin (DOX) is one of the most frequently used anticancer drugs in breast cancer treatment. However, clinical applications of DOX are restricted, largely due to the fact that its action disturbs the pro/antioxidant balance in both cancerous and non-cancerous cells. The aim of this study was to investigate the influence of fullerene (C60) in cell treatment by DOX on the proliferation of human breast cancer cells (MCF-7), concentration of metallothionein (MT) and superoxide dismutase (SOD), and SOD activity in these cells. The use of C60 in complexes with DOX causes a change in the level of cell proliferation of about 5% more than when caused by DOX alone (from 60⁻65% to 70%). The use of C60 as a DOX nanotransporter reduced the MT level increase induced by DOX. C60 alone caused an increase of SOD1 concentration. On the other hand, it led to a decrease of SOD activity. C60 in complex with DOX caused a decrease of the DOX-induced SOD activity level. Exposure of MCF-7 cells to DOX-C60 complexes results in a decrease in viable cells and may become a new therapeutic approach to breast cancer. The effects of C60 in complexes with DOX on MCF-7 cells included a decreased enzymatic (SOD activity) and nonenzymatic (MT) antioxidant status, thus indicating their prooxidant role in MCF-7 cells.

• Keywords
• breast tumors, doxorubicin, drug delivery systems, fullerene, nanoparticles, metallothionein, superoxide dismutase,
• MeSH
• Doxorubicin pharmacology   MeSH
• Fullerenes chemistry   MeSH
• Humans MeSH
• Metallothionein metabolism   MeSH
• MCF-7 Cells MeSH
• Nanoparticles chemistry   MeSH
• Cell Proliferation drug effects   MeSH
• Antineoplastic Agents pharmacology   MeSH
• Superoxide Dismutase-1 metabolism   MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH
• Names of Substances
• Doxorubicin MeSH
• Fullerenes MeSH
• Metallothionein MeSH
• Antineoplastic Agents MeSH
• SOD1 protein, human MeSH Browser
• Superoxide Dismutase-1 MeSH

Herein, we describe the preparation of liposomes with folate-targeting properties for the encapsulation of anti-sarcosine antibodies (antisarAbs@LIP) and sarcosine (sar@LIP). The competitive inhibitory effects of exogenously added folic acid supported the role of folate targeting in liposome internalization. We examined the effects of repeated administration on mice PC-3 xenografts. Sar@LIP treatment significantly increased tumor volume and weight compared to controls treated with empty liposomes. Moreover, antisarAbs@LIP administration exhibited a mild antitumor effect. We also identified differences in gene expression patterns post-treatment. Furthermore, Sar@LIP treatment resulted in decreased amounts of tumor zinc ions and total metallothioneins. Examination of the spatial distribution across the tumor sections revealed a sarcosine-related decline of the MT1X isoform within the marginal regions but an elevation after antisarAbs@LIP administration. Our exploratory results demonstrate the importance of sarcosine as an oncometabolite in PCa. Moreover, we have shown that sarcosine can be a potential target for anticancer strategies in management of PCa.

• MeSH
• Models, Biological MeSH
• Phosphatidylethanolamines MeSH
• Folic Acid metabolism   MeSH
• Humans MeSH
• Liposomes * chemistry   ultrastructure   MeSH
• Metallothionein metabolism   MeSH
• Disease Models, Animal MeSH
• Antibodies, Monoclonal administration & dosage   MeSH
• Mice MeSH
• Cell Line, Tumor MeSH
• Prostatic Neoplasms drug therapy   metabolism   pathology   MeSH
• Sarcosine antagonists & inhibitors   chemistry   MeSH
• Tumor Burden drug effects   MeSH
• Dose-Response Relationship, Drug MeSH
• Xenograft Model Antitumor Assays MeSH
• Zinc metabolism   MeSH
• Animals MeSH
• Check Tag
• Humans MeSH
• Male MeSH
• Mice MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Names of Substances
• dioleoyl phosphatidylethanolamine MeSH Browser
• Phosphatidylethanolamines MeSH
• Folic Acid MeSH
• Liposomes * MeSH
• Metallothionein MeSH
• Antibodies, Monoclonal MeSH
• Sarcosine MeSH
• Zinc MeSH