Metallothioneins and zinc in cancer diagnosis and therapy.
Metallothioneins (MTs) are involved in protection against oxidative stress (OS) and toxic metals and they participate in zinc metabolism and its homeostasis. Disturbing of zinc homeostasis can lead to formation of reactive oxygen species, which can result in OS causing alterations in immunity, aging, and civilization diseases, but also in cancer development. It is not surprising that altered zinc metabolism and expression of MTs are of great interest in the case of studying of oncogenesis and cancer prognosis. The role of MTs and zinc in cancer development is tightly connected, and the structure and function of MTs are strongly dependent on Zn²⁺ redox state and its binding to proteins. Antiapoptic effects of MTs and their interactions with proteins nuclear factor kappa B, protein kinase C, esophageal cancer-related gene, and p53 as well as the role of MTs in their proliferation, immunomodulation, enzyme activation, and interaction with nitric oxide are reviewed. Utilization of MTs in cancer diagnosis and therapy is summarized and their importance for chemoresistance is also mentioned.
Department of Chemistry and Biochemistry, Faculty of Agronomy, Mendel University in Brno, Brno, Czech Republic.
Sona
S
Krizkova
Marketa
M
Ryvolova
Jan
J
Hrabeta
Vojtech
V
Adam
Marie
M
Stiborova
Tomas
T
Eckschlager
Rene
R
Kizek
D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use; D017209:Apoptosis / Q000187:drug effects; D014408:Biomarkers, Tumor / Q000097:blood / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects; D006801:Humans; D056747:Immunomodulation; D008668:Metallothionein / Q000037:antagonists & inhibitors / Q000097:blood / Q000378:metabolism*; D058990:Molecular Targeted Therapy; D009363:Neoplasm Proteins / Q000037:antagonists & inhibitors / Q000097:blood / Q000378:metabolism; D009369:Neoplasms / Q000175:diagnosis* / Q000188:drug therapy* / Q000276:immunology / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects; D011379:Prognosis; D015032:Zinc / Q000009:adverse effects / Q000172:deficiency / Q000378:metabolism*
D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; D009363:Neoplasm Proteins; D009569:Nitric Oxide; D008668:Metallothionein; D015032:Zinc