The novel phospholipase C activator, m-3M3FBS, induces monocytic leukemia cell apoptosis.
We investigated the effect of the novel phospholipase C activator, m-3M3FBS, on the apoptosis of leukemic cells. m-3M3FBS inhibited the growth of the leukemic cell lines U937 and THP-1, but not primary monocytes. m-3M3FBS induced the apoptosis of U937 cells, which was accompanied by chromatin condensation and DNA fragmentation. Moreover, m-3M3FBS-induced apoptosis appeared to involve the down-regulation of anti-apoptotic Bcl-2, the up-regulation of pro-apoptotic Bax, the release of cytochrome c, and caspase activation. m-3M3FBS-induced apoptosis of U937 cells was also partly inhibited by BAPTA-AM and EGTA, indicating the involvement of intracellular calcium signaling on the apoptosis in U937 cells. The results of our study suggest that m-3M3FBS can be developed as a novel anti-leukemic agent.
Lee
Youl-Nam
YN
Medical Research Center for Cancer Molecular Therapy, College of Medicine, Dong-A University, Busan 602-714, South Korea.
Lee
Ha-Young
HY
Kim
Jae-Seok
JS
Park
Cheol
C
Choi
Yung Hyun
YH
Lee
Taehoon G
TG
Ryu
Sung Ho
SH
Kwak
Jong-Young
JY
Bae
Yoe-Sik
YS
D017209:Apoptosis / Q000187:drug effects*; D002470:Cell Survival; D015536:Down-Regulation; D006801:Humans; D007948:Leukemia, Monocytic, Acute / Q000473:pathology*; D009000:Monocytes / Q000187:drug effects; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000096:biosynthesis; D013449:Sulfonamides / Q000494:pharmacology*; D014407:Tumor Cells, Cultured; D015854:Up-Regulation; D051028:bcl-2-Associated X Protein; D000096926:Benzenesulfonamides
D019253:Proto-Oncogene Proteins c-bcl-2; D013449:Sulfonamides; D051028:bcl-2-Associated X Protein; C473783:2,4,6-trimethyl-N-(meta-3-trifluoromethylphenyl)benzenesulfonamide; D000096926:Benzenesulfonamides; C494826:BAX protein, human