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

doi:10.1016/j.bmc.2007.10.086

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

Department of Life Sciences

Research output: Contribution to journal › Article › peer-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 language	English
Pages (from-to)	1125-1132
Number of pages	8
Journal	Bioorganic and Medicinal Chemistry
Volume	16
Issue number	3
DOIs	https://doi.org/10.1016/j.bmc.2007.10.086
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

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1016/j.bmc.2007.10.086

Cite this

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title = "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.",

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author = "Kim, {Seung Hyun} and Oh, {Sang Mi} and Song, {Ju Han} and Daeho Cho and Le, {Quynh Manh} and Lee, {Suh Hee} and Cho, {Won Jea} and Kim, {Tae Sung}",

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.",

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AU - Cho, Daeho

AU - Le, Quynh Manh

AU - Lee, Suh Hee

AU - Cho, Won Jea

AU - Kim, Tae Sung

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N2 - 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.

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KW - Differentiation

KW - Indenoisoquinoline

KW - Leukemia

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

Abstract

Bibliographical note

Keywords

ASJC Scopus subject areas

UN SDGs

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