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

Seung Hyun Kim, Sang Mi Oh, Ju Han Song, Daeho Cho, Quynh Manh Le, Suh Hee Lee, Won Jea Cho, Tae Sung Kim

    Research output: Contribution to journalArticlepeer-review

    11 Citations (Scopus)

    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 languageEnglish
    Pages (from-to)1125-1132
    Number of pages8
    JournalBioorganic and Medicinal Chemistry
    Volume16
    Issue number3
    DOIs
    Publication statusPublished - 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

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