Induction of granulocytic differentiation in acute promyelocytic leukemia cells (HL-60) by 2-(allylthio) pyrazine.
Induction of hematopoietic differentiation in human promyelocytic leukemia cells (HL-60) by new synthetic drugs or natural products has recently been recognized as a new strategy in the identification and testing of potential cancer chemopreventive and/or chemotherapeutic agents. 2-(Allythio) pyrazine (2-AP) is a pyrazine derivative of allysulfide, which has been suggested to be a potential cancer chemopreventive agent in previous in vivo and in vitro experiments. In the present study, we have investigated the inducing effect of granulocytic differentiation in HL-60 cells by 2-AP. Treatment of HL-60 cells with various concentrations of 2-AP (1-100 microM) for 7 days showed the induction of granulocytic differentiation following both morphological examination and NBT (nitroblue tetrazolium) testing (up to 40 and 52%, respectively). The expressions of bcl-2 and c-myc were down-regulated during granulocytic differentiation of HL-60 cells (up to 40%). The immunoblots for G1 cyclins in the G1-S phase transition (cyclin D1 and E) showed a progressive decrease of their expressions in both concentration- and time-dependent manners (up to 30 and 50%, respectively). These results suggest that 2-AP could induce the differentiation of HL-60 cells and might have potent cancer chemoprevention and/or chemotherapy roles in human leukemias.
Kong
G
G
Department of Pathology, College of Medicine, Hanyang University, Seoul, South Korea. gkong@email.hanyang.ac.kr
Lee
S J
SJ
Kim
H J
HJ
Surh
Y J
YJ
Kim
N D
ND
D016588:Anticarcinogenic Agents / Q000494:pharmacology*; D002454:Cell Differentiation / Q000187:drug effects; D056741:Cyclin D; D019927:Cyclin E / Q000032:analysis; D016213:Cyclins / Q000032:analysis; D015536:Down-Regulation; D006098:Granulocytes / Q000166:cytology / Q000187:drug effects*; D018922:HL-60 Cells / Q000187:drug effects*; D006801:Humans; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000032:analysis; D016271:Proto-Oncogene Proteins c-myc / Q000032:analysis; D011719:Pyrazines / Q000494:pharmacology*
C104935:2-(allylthio)pyrazine; D016588:Anticarcinogenic Agents; D056741:Cyclin D; D019927:Cyclin E; D016213:Cyclins; D019253:Proto-Oncogene Proteins c-bcl-2; D016271:Proto-Oncogene Proteins c-myc; D011719:Pyrazines