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

Authors
Kim, Seung HyunOh, Sang MiSong, Ju HanCho, DaehoLe, Quynh ManhLee, Suh-HeeChob, Won-JeaKim, Tae Sung
Issue Date
1-2월-2008
Publisher
PERGAMON-ELSEVIER SCIENCE LTD
Keywords
All-trans retinoic acid; Differentiation; Indenoisoquinoline; Leukemia
Citation
BIOORGANIC & MEDICINAL CHEMISTRY, v.16, no.3, pp.1125 - 1132
Indexed
SCIE
SCOPUS
Journal Title
BIOORGANIC & MEDICINAL CHEMISTRY
Volume
16
Number
3
Start Page
1125
End Page
1132
URI
https://scholar.korea.ac.kr/handle/2021.sw.korea/124104
DOI
10.1016/j.bmc.2007.10.086
ISSN
0968-0896
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 e-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. (c) 2007 Elsevier Ltd. All rights reserved.
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