Indeno[1,2-c]isoquinolines as enhancing agents on all-trans retinoic acid-mediated differentiation of human myeloid leukemia cells.

Abstract

Induction of differentiation is a new and promising approach to cancer therapy, well illustrated by the treatment of acute myeloid leukemia with all-trans retinoic acid (ATRA). Using combination of ATRA and chemotherapy, adverse effects such as retinoic acid syndrome have decreased, and long-term survival has improved. In this study, we demonstrated that the indeno[1,2-c]isoquinolines markedly enhanced differentiation of human myeloid leukemia HL-60 and NB4 cells when simultaneously combined with a low dose of ATRA. Of the tested compounds, 6-(4-methoxybenzyl)-2,11-dimethyl-6H,11H-indeno[1,2-c]isoquinolin-5-one (IIQ-16), an indeno[1,2-c]isoquinoline derivative, showed the highest differentiation-enhancing activity via a pathway involved with protein kinase C, extracellular signal-regulated kinase, and c-Jun N-terminal kinase. The ability to enhance the differentiation potential of ATRA by IIQ-16 may improve outcomes in the therapy of acute promyelocytic leukemia.

• Authors: Seung Hyun Kim, Sang Mi Oh, Ju Han Song, Daeho Cho, Quynh Manh Le, Suh-Hee Lee, Won-Jea Cho, Tae Sung Kim
• Journal: Bioorganic & medicinal chemistry (Bioorg Med Chem) Vol. 16 Issue 3 Pg. 1125-32 (Feb 01 2008) ISSN: 1464-3391 [Electronic] England
• PMID: 18024133 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Indenes
• Isoquinolines
• Tretinoin

Topics

• Cell Differentiation (drug effects)
• Cell Line, Tumor
• Cell Survival (drug effects)
• Humans
• Indenes (chemistry)
• Isoquinolines (chemical synthesis, chemistry, pharmacology)
• Leukemia, Myeloid (pathology)
• Molecular Structure
• Structure-Activity Relationship
• Tretinoin (pharmacology)