Induction of differentiation and apoptosis in human promyelocytic leukemia HL60 cell line by a new type of steroids.

Abstract

Mer-NF8054X is a new type of steroid whose structure has been established as 11-oxo-18, 22-cycloergosta-6, 8(14)-diene-3beta, 5beta, 9beta, 23S-tetraol (an 18, 22-cycloergostane), which has been reported to have antifungal activity against Aspergillus fumigatus. However, other biological activities are unknown. Herein, we reported that Mer-NF8054X inhibited cell growth of HL60 human leukemia cells, when used either singly or in combination with retinoic acid (RA). In addition, Mer-NF8054X alone induced differentiation and apoptosis of HL60 cells. The induction of differentiation of HL60 cells by Mer-NF8054X was synergistic in combination with RA. On the other hand, Emesterone A, an analogue of Mer-NF8054X which is missing a hydroxy residue from the third position, showed much lower activity than Mer-NF8054X on the inhibition of cell growth and the induction of cell differentiation and apoptosis. However, Emesterone B, an analogue of Emesterone A which is missing a hydroxy residue from the fifth position, showed higher activity than Emesterone A but lower activity than Mer-NF8054X when examined for the inhibition of cell growth and the induction of cell differentiation and apoptosis. These results suggested that Mer-NF8054X and its analogs may be a new type of differentiation inducing agent. The hydroxy residue at the third position or fifth position in Mer-NF8054X may be necessary, but not essential, for inhibition of growth and induction of both differentiation and apoptosis of HL60 cells. In addition, Mer-NF8054X enhanced the differentiation of HL60 cells induced by RA. Based on these results, Mer-NF8054X may have utility in the clinic in combination with RA for leukemia patients.

• Authors: N Takahashi, T Fukui, A Iwahori, Y Kubo, T Hosoe, K Kawai
• Journal: Experimental cell research (Exp Cell Res) Vol. 245 Issue 2 Pg. 313-20 (Dec 15 1998) ISSN: 0014-4827 [Print] United States
• PMID: 9851872 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright 1998 Academic Press.

Chemical References

• Antineoplastic Agents
• Ketosteroids
• emesterone A
• emesterone B
• Mer NF8054X
• Fenretinide
• Tretinoin
• DNA

Topics

• Antineoplastic Agents (pharmacology, therapeutic use)
• Apoptosis (drug effects)
• Ascomycota
• Aspergillus
• Cell Differentiation (drug effects)
• Cell Division (drug effects)
• Cell Size (drug effects)
• DNA (biosynthesis)
• DNA Fragmentation (drug effects)
• Dose-Response Relationship, Drug
• Drug Synergism
• Fenretinide (pharmacology)
• HL-60 Cells
• Humans
• Ketosteroids (pharmacology, therapeutic use)
• Leukemia, Myeloid (drug therapy, pathology)
• Macrophages (cytology)
• Monocytes (cytology)
• Tretinoin (pharmacology)