Nonradioactive Iodide Effectively Induces Apoptosis in Genetically Modified Lung Cancer Cells

Apoptosis is a process of deliberate life relinquishment by a cell in a multicellular organism. It is one of the main types of programmed cell death (PCD), and involves an orchestrated series of biochemical events leading to a characteristic cell morphology and death. The apoptotic process is executed in such a way as to safely dispose of cell corpses and fragments...Apoptosis was distinguished from traumatic cell death in 1972 by Andrew H. Wyllie while studying tissues with electron microscopes[1]. He called this process of natural cell death apoptosis, from the use of this word in an ancient Greek poem to mean "falling off" and its connotations of leaves falling from a tree.


Access to full article re Nonradioactive Iodine
Cancer Research 63, 5065-5072, August 15, 2003] © 2003 American Association for Cancer Research

ABSTRACT:  We assessed a nonradioactive approach to induce apoptosis in non-small cell lung cancer by a novel iodide uptake and retention mechanism. To enhance tumor apoptosis, we transduced non-small cell lung cancer cells with retroviral vectors containing the sodium iodide symporter (NIS) and thyroperoxidase (TPO) genes. Expression of NISand TPO facilitated concentration of iodide in tumors. As a consequence of the marked increase in intracellular levels of iodide, apoptosis was seen in >95% of NIS/TPO-modified lung cancer cells. Intraperitoneal injection of potassium iodide resulted in significant tumor volume reduction in NIS/TPO-modified tumor xenografts without apparent adverse effects in SCID mice. Iodide induced an increase in the level of reactive oxygen species. Iodide-induced apoptosis is sensitive to N-acetylcysteine inhibition, suggesting an important role by reactive oxygen species in this apoptotic process. In addition, iodide-induced apoptosis is associated with overexpression of CDKN1A (p21/Waf1)and down-regulation of survivin at both mRNA and protein levels. This is the first report demonstrating that a therapeutic dose of nonradioactive iodide has potent efficacy and high selectivity against lung cancer when used in combination with genetic modification of cancer cells to express the NIS/TPOgenes.