The thymus extract Thymex-L potentiates the retinoic acid-induced differentiation of the human myeloid leukemia cell line HL-60.
The human promyelocytic cell line HL-60 can be differentiated with retinoic acid (RA) along the granulocytic pathway. Numerous studies have identified many synergistic combinations of RA with cytostatics, cytokines and other inducers. A combination of RA with the crude thymus extract Thymex-L increased differentiation of HL-60 cells as confirmed by two functional assays and morphology, whereas the extract itself did not show any effect. The functional markers phagocytosis-associated chemiluminescence and nitroblue tetrazolium reduction were more enhanced (up to 4-fold with 1000 micrograms/ml Thymex-L) than morphology. The effect was found over a wide RA concentration range (10(-11) - 10(-6) M) and was dependent on extract concentration. The half-maximal induction of both functional markers was reached at 400 micrograms/ml. To achieve the same effect with the combination in comparison with RA alone, an RA dose reduction of about 100-fold was estimated. The effect was also seen when the cells were pretreated with the thymus extract for two days. The enhancement of RA action by Thymex-L was not correlated with an increase of extracellular or intracellular RA concentration. The active compound in Thymex-L is heat stable and bigger than 5 kDa as confirmed by gelfiltration. The defined thymus peptides thymosin alpha 1, prothymosin alpha 1 and thymopentin were unable to synergistically enhance HL-60 differentiation. These data suggest that the treatment with a thymus extract can increase the sensitivity of HL-60 cells for RA. This may have clinical implications.
Schulze-Forster
K
K
Department of Pharmaceutical Biochemistry, Free University of Berlin, Germany.
Eckert
K
K
Maurer
H R
HR
D002454:Cell Differentiation / Q000187:drug effects*; D004357:Drug Synergism; D006801:Humans; D007951:Leukemia, Myeloid / Q000473:pathology; D013949:Thymus Extracts / Q000737:chemistry / Q000494:pharmacology*; D014212:Tretinoin / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
D013949:Thymus Extracts; C092820:Thymex-L; D014212:Tretinoin