Thiophosphate induces apoptosis in human leukemia cell lines
Apoptosis is a form of self-regulated cell death which differs from necrosis (1). The characteristic morphological changes of apoptosis include membrane blebbing, chromatin condensation and the formation of apoptotic bodies. In addition, apoptotic cells undergo DNA double strand cleavage into fragments of multiples of about 185–200 bp resulting in a characteristic laddering pattern on agarose gel electrophoresis (2–4). Apoptosis is necessary for normal embryonic and tissue differentiation (3, 5, 6). Cell death in tumors, whether spontaneous or treatment-induced, occurs predominantly via apoptosis rather than necrosis (7, 8).
Thiophosphate is a sulfur-substituted analog of orthophosphate that is an essential component of commonly used hydrolysis-resistant nucleotide analogs such as ATPgS and GTPgS as well as thiophosphorylated forms of DNA that are popular in antisense transfection studies. In a study of the growth suppressing effect of ATPgS on human promyelocytic HL-60 cells (9), we noted that thiophosphate, a breakdown product of ATPgS, independently inhibited cell growth. We investigated the nature of the thiophosphate effect on HL-60 cell proliferation and found that this effect occurs via the induction of apoptosis.