EXPRESSION PROFILING OF ADAPHOSTIN REGULATED GENES IN MULTIPLE HUMAN LUNG CARCINOMA CELL LINES

Abstract

The preclinical agent adaphostin has been demonstrated to induce diverse mechanisms of action in human hematopoietic tumor cell lines. This led to the examination of adaphostin-induced transcriptional changes in human lung carcinoma cell lines exhibiting similar adaphostin sensitivity. Transcriptional profiling of 4 adaphostin treated lung carcinoma cell lines using microarray technology identified induction of heme oxygenase 1 and 12 related genes, the majority of which associated with intracellular oxidative stress, specifically reactive oxygen species (ROS). Through the use of RT-PCR and Western blot analysis, induction of many of these genes was confirmed. These data indicate that adaphostin treatment in these cell lines elicited an oxidative stress response, through a means distinct from that demonstrated in leukemia cell lines. A proposed mechanism involving the activation of Nrf2/ARE pathway and subsequent induction of cytoprotective genes by adaphostin has been formulated for these lung carcinoma cell lines.