Open AccessInduction of terminal differentiation in human promyelocytic leukemia cells by tumor-promoting agents.
Author(s) -
Eliezer Huberman,
Michael F. Callaham
Publication year - 1979
Publication title -
proceedings of the national academy of sciences of the united states of america
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.011
H-Index - 771
eISSN - 1091-6490
pISSN - 0027-8424
DOI - 10.1073/pnas.76.3.1293
Subject(s) - phorbol , cellular differentiation , myeloid leukemia , myeloid , cell culture , cell growth , tetradecanoylphorbol acetate , leukemia , acute promyelocytic leukemia , myeloid cells , chemistry , microbiology and biotechnology , cell , biology , cancer research , biochemistry , immunology , retinoic acid , protein kinase c , signal transduction , genetics , gene
Human promyelocytic leukemia cells (HL-60) were induced to differentiate into mature cells by the tumor-promoting agent phorbol-12-myristate-13-acetate and other related phorbol diesters. Differentiation was determined by an increase in the percent of myelocytes, metamyelocytes, and other mature myeloid cells as well as by an increase in the percent of phagocytizing cells. Induction of differentiation could be determined after 2 days of treatment with phorbol-12-myristate-13-acetate at a dose as low as 6 X 10(11) M. A correlation was found between reported tumor-promoting activity of a series of phorbol esters and their ability to induce myeloid differentiation and to inhibit cell growth. It is suggested that tumor-promoting agents like chemicals that induce terminal differentiation in these cells, at extremely low concentrations, may be used as a tool in the study of the control of cell growth, cell differentiation, and malignancy in human leukemic cells.