Response of human erythroleukemia cells to heteroarotinoids

Abstract

All trans‐Retinoic acid (RA) is a naturally occurring molecule that binds to retinoic acid receptors and contributes to proliferation regulation. Heteroarotinoids (Hets) are synthetic structural analogues to RA, defined as systems with one aromatic ring and one heteroatom that exhibit lower toxicity as well as increased biological activity. In this study, human erythroleukemia cells were cultured for 72 h and chemically treated for the latter 48 h with Het 1, Het 4, thapsigargin (TH) for positive apoptosis control, RA for biological activity standard, and no treatment for control. Cells were assayed for viability and growth inhibition using trypan blue exclusion, relative levels of apoptosis induction using Hoechst stain and propidium iodide with fluorescent microscopy, and tissue transglutaminase (tTG) expression. RA showed the least growth inhibition and apoptosis induction relative to Het 1 and Het 4. Het 1 and Het 4 showed approximately equivalent growth inhibition relative to control, three‐fold greater than RA. Het 1 and Het 4 resulted in a 89% and 77% apoptosis induction relative to TH respectively. Het 1 and Het 4 also showed a 4‐5‐fold increase in apoptosis relative to control. Both Het 1 and Het 4 contain sulfur heteroatoms and the increased biological activity of Het 1 is attributed to the presence of a thiourea link. Relative to other modifications, changes to the end of the side chain made virtually no enhancement. Support for this research was supplied by the College of Health, Science and Environment and Faculty/Student Research Grant program of Slippery Rock University.