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.
Original language | English |
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Pages (from-to) | 1125-1132 |
Number of pages | 8 |
Journal | Bioorganic and Medicinal Chemistry |
Volume | 16 |
Issue number | 3 |
DOIs | |
Publication status | Published - 2008 Feb 1 |
Bibliographical note
Funding Information:This study was supported by grants from the Korea Health 21 R&D Project, Ministry of Health and Welfare (01-PJ10-PG6-01GN16-0005) and the Seoul Research and Business Program (10582) to T.S. Kim, and a grant from the Korea Research Foundation (KRF-2004-C00325) to W.-J. Cho.
Keywords
- All-trans retinoic acid
- Differentiation
- Indenoisoquinoline
- Leukemia
ASJC Scopus subject areas
- Biochemistry
- Molecular Medicine
- Molecular Biology
- Pharmaceutical Science
- Drug Discovery
- Clinical Biochemistry
- Organic Chemistry