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.
authors.affiliation: School of Life Sciences and Biotechnology, Korea University, Seoul, Republic of Korea.
authors.forename: Seung Hyun
authors.initials: SH
authors.lastname: Kim
authors.forename: Sang Mi
authors.initials: SM
authors.lastname: Oh
authors.forename: Ju Han
authors.initials: JH
authors.lastname: Song
authors.forename: Daeho
authors.initials: D
authors.lastname: Cho
authors.forename: Quynh Manh
authors.initials: QM
authors.lastname: Le
authors.forename: Suh-Hee
authors.initials: SH
authors.lastname: Lee
authors.forename: Won-Jea
authors.initials: WJ
authors.lastname: Cho
authors.forename: Tae Sung
authors.initials: TS
authors.lastname: Kim
mesh_terms: 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*
chemical_list: D007192:Indenes; D007546:Isoquinolines; D014212:Tretinoin