DISTINCT EFFECT OF H2O2 IN HEALTH AND UNHEALTHY HEMATOPOIETIC CELLS SURVIVAL

Abstract

In the last years, many data has suggested the participation of oxidative stress in the regulation of hematopoietic cell homeostasis. Hematopoietic cells are particularly vulnerable to reactive oxygen species (ROS) in a concentration‐dependent manner. It is known that constitutively ROS levels differ between normal and malignant cells. In this respect it is the ideal balance in the redox status for both cell types in order to selectively cause death of cancer but not normal cells. In this work it was induced a pro‐oxidant environment by stimulating murine and fresh human umbilical cord blood (health models) as well as HL‐60 leukemic cells (unhealthy model) with different concentrations (0, 1, 5 and 10 μM) of hydrogen peroxide (H2O2) in vitro. It was observed that H2O2 (5 μM) induced cancer but not normal cells death (28% versus 0,5%). However, HL‐60 hematopoietic stem cells has increased in percentage at the same time progenitors cells diminished. In addition clonogenic capacity was great affected on these cells, enabling to generate myeloid clones. Differentiation was not modulated by the H2O2 in any cell type. HL‐60 loss viability had the participation of phosphor‐AKT which expression has diminished significantly. In summary, we found that at low concentration, H2O2 is able to kill hematopoietic cancer cells without affect normal cells.Supporting: FAPESP