INDUCING DIFFERENTIATION OF TRANSFORMED-CELLS WITH HYBRID POLAR COMPOUNDS - A CELL CYCLE-DEPENDENT PROCESS

Transformed cells do not necessarily lose their capacity to differenti ate. Various agents can induce many types of neoplastic cells to termi nal differentiation. Among such inducers, a particularly potent group consists of hybrid polar compounds; hexamethylene bisacetamide (HMBA) is the prototype of this group. With virus-transformed murine erythrol eukemia cells as a model, HMBA was shown to cause these cells to arres t in G(1) phase and express globin genes. This review focuses on HMBA- induced modulation of factors regulating G(1)-to-S phase progression, including a decrease in the G(1) cyclin-dependent kinase cdk4, associa ted with inhibition of phosphorylation of the retinoblastoma protein p RB and possibly other related proteins that, in turn, sequester factor s required for initiation of DNA synthesis; this provides a possible m echanism for HMBA-induced terminal cell division. Evidence that hybrid polar compounds have therapeutic potential for cancer treatment will also be reviewed.