Induction of apoptosis and necrosis by zinc in human thyroid cancer cell lines.
Zinc at concentrations of 150, microM or higher induced necrosis as well as apoptosis in thyroid cancer cell lines. Necrosis was induced by zinc in a dose-dependent manner, whereas apoptosis did not increase at higher concentrations of zinc. The expression of the antiapoptotic protein phosphorylated Bad was markedly increased, whereas the expression of the proapoptotic proteins Bax and Bad decreased following Zn(2+) exposure. Zn(2+) induced rapid degradation of IkappaB, and an increase in the binding of nuclear transcription factor-kappaB (NF-kappaB). These observations indicate that antiapoptotic pathways were activated in thyroid cancer cells following exposure to Zn(2+). This may be a self-defence mechanism against apoptosis and may underlie the general resistance of thyroid cancer cells to apoptotic stimuli. Zinc may be a potential cytotoxic agent for the treatment of thyroid cancer.
Iitaka
M
M
Department of Internal Medicine 4, Saitama Medical School, 38 Morohongo, Moroyama, Iruma-gun, Saitama 350-0495, Japan.
Kakinuma
S
S
Fujimaki
S
S
Oosuga
I
I
Fujita
T
T
Yamanaka
K
K
Wada
S
S
Katayama
S
S
D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D015415:Biomarkers / Q000032:analysis; D015153:Blotting, Western; D002352:Carrier Proteins / Q000378:metabolism; D002460:Cell Line; D004396:Coloring Agents; D004305:Dose-Response Relationship, Drug; D016328:NF-kappa B / Q000378:metabolism; D009336:Necrosis; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2; D051381:Rats; D013964:Thyroid Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology*; D015032:Zinc / Q000627:therapeutic use*; D051028:bcl-2-Associated X Protein; D051025:bcl-Associated Death Protein
C494821:Bad protein, rat; C494828:Bax protein, rat; D015415:Biomarkers; D002352:Carrier Proteins; D004396:Coloring Agents; D016328:NF-kappa B; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D051028:bcl-2-Associated X Protein; D051025:bcl-Associated Death Protein; D015032:Zinc