HMBA inhibits growth and induces differentiation of astrocytes from neonatal rat brain

HMBA, a potent differentiation inducer belonging to the class of hybrid polar compounds, inhibited the growth of astrocytes from neonatal rat brain. At a concentration of 5.0 mM, which is necessary for growth inhibition and differentiation of a number of leukemic and solid tumour cell lines, astrocyte proliferation was reduced by 74.5+/-5.5%. On HMBA treatment astrocyte morphology changed from flat polygonal with phase translucent cytoplasm to compact retracted appearance with phase dark cytoplasm. HMBA also increased expression of GFAP, a marker for mature astrocytes. HMBA thus induces both morphological and biochemical differentiation of astrocytes. Like dbcAMP and staurosporine, two other known differentiation inducers of astrocytes, HMBA was also found to induce expression of the immediate early gene c-fos. However, unlike dbcAMP and staurosporine, which also induce fra-1, HMBA repressed cycloheximide-induced fra-1 gene expression. (C) 1999 Lippincott Williams & Wilkins.