Differentiation of human myeloid leukemic cells by phorbol esters: correlation with tumor promotion

The effect of the plant diterpenes, phorbol derivatives and mezerein, on differentiation of various human myeloid leukemic cells to macrophages was determined. The results indicate that, within the group of phorbol esters tested, a correlation exists between the potency of the compounds as inducers of differentiation and their reported potency as tumor promoters. However, mezerein and 12-O-retinoylphorbol 13-acetate, which promote tumors only weakly or not at all, were found to be efficient inducers. The efficiency of all the active phorbol derivatives, including the weak inducers, also known to be weak promoters, could be potentiated by pretreatment of the cells with retinoids, compounds which have been reported to inhibit tumor promotion. Similar results were obtained in 3 different established cell lines, as well as in short-term cultures of cells obtained from patients with acute myeloid leukemia. The results suggest that the activities of the diterpenes as tumor promoters and inducers of differentiation are not necessarily linked. Moreover, certain conditions which are unfavorable for tumor promotion may not affect or even potentiate induction of differentiation.