The Apoptotic Effect of Extracellular Zinc Sequestration on HT29/219

Zn (II) is an important regulator of caspase-3, as well as an antioxidant, microtubule stabilizer, growth cofactor, and anti-inflammatory agent. Over the past 30 years, many researchers have demonstrated the important role of Zn (II) in a variety of physiological processes, including growth and development, maintenance and priming of the immune system, and in tissue repair and regeneration. In this study, we present evidence that chelation of extracellular zinc by diethylenetriaminepentacetic acid (DTPA) in different concentrations causes cell death in carcinoma cell lines, HT29/219 and SW742. Hoechst 33258 staining revealed that cell death was mainly by apoptosis. Additionally, significant increases in the activity of caspase-3 and-9 were observed in both cell lines. Caspase-8 activation was negligible in both cell lines. The cytotoxicity/apoptotic effect of DTPA was inhibited significantly by Zn (II), Cu (II) and N-Acetyl-L-Cysteine (NAC) (P<0.05). Therefore, DTPA, the membrane-impermeable metal ion chelator, induces apoptosis through the depletion of extracellula