Abstract
The simultaneous administration of the DNA topoisomerase II inhibitor etoposide (0.15 mM) and 1,25-dihydroxyvitamin D3 (VD3) (10 nM) synergistically induced the differentiation of HL-60 human promyelocytic leukemia cells. Similar results were obtained using U-937 human promonocytic cells, or the topoisomerase II inhibitors doxorubicin (15 nM) and mitoxantrone (2.5 nM). When sequential treatments were used, pre-incubation with VD3 had little effect on the subsequent action of etoposide, while pre-incubation with etoposide greatly potentiated the subsequent action of VD3. In addition, etoposide treatment stimulated VD3 binding activity and increased VD3 receptor mRNA and protein levels. The increase in hormone receptor expression may explain, at least in part, the capacity of topoisomerase inhibitors to potentiate the differentiation inducing activity of VD3.
Similar content being viewed by others
References
Hussler MR, McCain N: Basic and clinical concepts related to vitamin D metabolism and action. N Engl J Med 297: 974–983, 1977
Norman AW, Roth J, Orci L: The vitamin D endocrine system: Steroid metabolism, hormone receptors and biological response (calcium binding proteins). Endocr Rev 3: 331–366, 1982
Abe EC, Miyaura C, Sakagami M, Takeda M, Konno K, Yakamazi S, Yoshiki S, Suda T: Differentiation of mouse leukemia cells induced by 1 alpha, 25-dihydroxyvitamin D3. Proc Natl Acad Sci USA 78: 4990–4994, 1981
Miyaura C, Abe E, Kuribayashi T, Tanaka H, Konno K, Nishii Y, Suda T: 1 alpha, 25-dihydroxyvitamin D3 induces differentiation of human myeloid leukemia cells. Biochem Biophys Res Commun 102: 937–943, 1981
Honma Y, Honzuni M, Abe M, Kunio K, Fukushima M, Hata S, Nishii Y, DeLuca HF, Suda T: 1 alpha, 25-dihydroxyvitamin D3 and 1 alpha-hydroxyvitamin D3 prolong survival time of mice inoculated with myeloid leukemia cells. Proc Natl Acad Sci USA 80: 201–204, 1983
Koeffler HP, Hirji K, Itri L: 1,25-dihydroxyvitamin D3: In vivo and in vitro effects on human preleukemic and leukemic cells. Cancer Treat Rep 69: 1399–1407, 1985
Bertrand R, Solary E, Jenkins J, Pommier Y: Apoptosis and its modulation in human promyelocytic HL-60 cells treated with DNA topoisomerase I and II inhibitors. Exp Cell Res 207: 388–397, 1993
García-Bermejo L, Pérez C, Vilaboa NE, De Blas E, Aller P: cAMP increasing agents attenuate the generation of apoptosis by etoposide in promonocytic leukemia cells. J Cell Sci 111: 637–644, 1998
Rius C, Zorrilla AR, Cabañas C, Mata F, Bernabeu C, Aller P: Differentiation of human promonocytic leukemia U-937 cells with DNA topoisomerase II inhibitors: Induction of vimentin gene expression. Mol Pharmacol 39: 442–448, 1991
Nakaya K, Chou S, Kaneko M, Nakamura Y: Topoisomerase inhibitors have potent differentiation-inducing activity for human and mouse myeloid leukemia cells. Jpn J Cancer Res 82: 184–191, 1991
Jing Y, Hashimoto S, Nakajo S, Nakaya K: Topoisomerase inhibitors potentiate the effect of retinoic acid on cell growth inhibition and induction of differentiation of leukemia HL-60 cells. Leukemia Res 18: 299–304, 1994
Schreibert E, Matthias P, Muller MM, Schaffner W: Identification of a novel lymphoid specific octamer binding protein (OTF-2B) by proteolytic clipping bandshift assay (PCBA) EMBO J 7: 4221–4229, 1988
Bradford MM: A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal Biochem 72: 248–254, 1976
Vilaboa NE, Calle C, Perez C, de Blas E, Garcia-Bermejo L, Aller P: cAMP increasing agents prevent the stimulation of heat-shock protein 70 (HSP 70) gene expression by cadmium chloride in human myeloid cell lines. J Cell Science 108: 2877–2883, 1995
Vilaboa NE, García-Bermejo L, Pérez C, De Blas E, Calle C, Aller P: Heat-shock and cadmium chloride increase the vimentin mRNA and protein levels in U-937 human promonocytic cells. J Cell Sci 110: 201–207, 1997
Baker AP, McDonnell DP, Hughes M, Crisp TM, Mangelfort DJ, Haussler MR, Pike JW, Shine JW, O´Malley BW: Cloning and expression of full-length cDNA encoding human vitamin D receptor. Proc Natl Acad Sci USA 85: 3294–3298, 1988
Alonso S, Minty A, Borlet Y, Buckingham M: Comparison of three actin-coding sequences in the mouse: Evolutionary relationships between actin genes and warm-blood vertebrates. J Mol Evol 23: 1–22, 1986
Rius C, Aller P: Modulation of ornithine decarboxylase gene transcript levels by differentiation inducers in human promyelocytic leukemia HL60 cells. Cell Differ Dev 28: 39–46, 1989
Chen A, Licht JD, Wu Y, Hellinger N, Scher W, Waxman S: Retinoic acid is required for and potentiates differentiation of acute promyelocytic leukemia cells by nonretinoid agents. Blood 84: 2122–2129, 1994
Makishima M, Okabe-Kado J, Honma Y: Growth inhibition and differentiation induction in human monoblastic leukaemia cells by 1 alpha-hydroxyvitamin D derivatives and their enhancement by combination with hydroxyurea. Br J Cancer 77: 33–39, 1998
Pérez C, Vilaboa NE, Aller P: Etoposide-induced differentiation of U937 promonocytic cells: AP-1-dependent gene expression and protein kinase C activation. Cell Growth Differ 5: 949–955, 1994
Aihara H, Asaoka Y, Yoshida K, Nishikuza Y: Sustained activation of protein kinase C is essential to HL-60 cell differentiation to macrophage. Proc Natl Acad Sci USA 88: 11062–11066, 1991
Liebermann DA, Gregory B, Hoffman B: AP-1 (Fos/Jun) transcription factors in hematopoietic differentiation and apoptosis. Int J Oncol 12: 685–700, 1998
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Torres, R., Calle, C., Aller, P. et al. Etoposide stimulates 1,25-dihydroxyvitamin D3 differentiation activity, hormone binding and hormone receptor expression in HL-60 human promyelocytic cells. Mol Cell Biochem 208, 157–162 (2000). https://doi.org/10.1023/A:1007089632152
Issue Date:
DOI: https://doi.org/10.1023/A:1007089632152