Indeno[1,2-c]isoquinolines as enhancing agents on all-trans retinoic acid-mediated differentiation of human myeloid leukemia cells.
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.
Kim
Seung Hyun
SH
School of Life Sciences and Biotechnology, Korea University, Seoul, Republic of Korea.
Oh
Sang Mi
SM
Song
Ju Han
JH
Cho
Daeho
D
Le
Quynh Manh
QM
Lee
Suh-Hee
SH
Cho
Won-Jea
WJ
Kim
Tae Sung
TS
D002454:Cell Differentiation / Q000187:drug effects*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D006801:Humans; D007192:Indenes / Q000737:chemistry*; D007546:Isoquinolines / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D007951:Leukemia, Myeloid / Q000473:pathology*; D015394:Molecular Structure; D013329:Structure-Activity Relationship; D014212:Tretinoin / Q000494:pharmacology*
D007192:Indenes; D007546:Isoquinolines; D014212:Tretinoin