Enhancing effect of indirubin derivatives on 1,25-dihydroxyvitamin D3- and all-trans retinoic acid-induced differentiation of HL-60 leukemia cells.
The induction of differentiation represents a new and promising approach to cancer therapy, well illustrated by the treatment of acute promyelocytic leukemia (APL) with 1,25-dihydroxyvitamin D3 [1,25-(OH)2D3] or all-trans retinoic acid (ATRA). Using combinations of low, nontoxic concentrations of either 1,25-(OH)2D3 or ATRA and differentiation-enhancing chemicals, adverse effects such as hypercalcemic effects have been ameliorated, and long-term survival has been improved. Indirubin has been demonstrated to exert anti-leukemic effects in cases of chronic myelocytic leukemia. Previously, we synthesized a series of indirubin derivatives and evaluated their anti-proliferative properties against cancer cells. In this study, we determined the enhancing activities of these derivatives on 1,25-(OH)2D3- and ATRA-induced differentiation of human promyelocytic leukemia HL-60 cells. Importantly, some of these derivatives were found to synergistically enhance the differentiation of HL-60 cells in a concentration-dependent manner when coupled with low doses of either 1,25-(OH)2D3 or ATRA. The ability of indirubin derivatives to enhance the differentiation potential of 1,25-(OH)2D3 or ATRA may improve the ultimate outcomes of APL therapy.
Kim
Seung Hyun
SH
School of Life Sciences and Biotechnology, Korea University, Seoul 136-701, Republic of Korea.
Kim
Si-Wouk
SW
Choi
Soo Jeong
SJ
Kim
Yong-Chul
YC
Kim
Tae Sung
TS
D000903:Antibiotics, Antineoplastic / Q000494:pharmacology*; D002117:Calcitriol / Q000494:pharmacology*; D002454:Cell Differentiation / Q000187:drug effects*; D019070:Cell Lineage / Q000187:drug effects; D004357:Drug Synergism; D018922:HL-60 Cells; D006801:Humans; D019044:Image Cytometry; D007211:Indoles / Q000494:pharmacology; D014212:Tretinoin / Q000494:pharmacology*
D000903:Antibiotics, Antineoplastic; D007211:Indoles; D014212:Tretinoin; D002117:Calcitriol; C027185:indirubin