Premium
Induction of apoptosis by vitamin D 3 analogue EB1089 in NCI‐H929 myeloma cells via activation of caspase 3 and p38 MAP kinase
Author(s) -
Park Woo Hyun,
Seol Jae Goo,
Kim Eun Shil,
Hyun Jung Mi,
Jung Chul Won,
Lee Chung Choo,
Binderup Lise,
Koeffler H. Phillip,
Kim Byoung Kook,
Lee Young Yiul
Publication year - 2000
Publication title -
british journal of haematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.907
H-Index - 186
eISSN - 1365-2141
pISSN - 0007-1048
DOI - 10.1046/j.1365-2141.2000.02046.x
Subject(s) - apoptosis , mapk/erk pathway , p38 mitogen activated protein kinases , kinase , annexin , cell cycle , caspase , cell growth , microbiology and biotechnology , biology , chemistry , cancer research , programmed cell death , biochemistry
EB1089, a novel 1,25‐dihydroxyvitamin D 3 analogue, has been known to have potent antiproliferative properties in a variety of malignant cells both in vitro and in vivo . In the present study, we analysed the effect of EB1089 on NCI‐H929 human myeloma cells. EB1089 inhibited cell growth of NCI‐H929 and efficiently induced the G 1 phase arrest of the cell cycle in a dose‐dependent manner. We could also detect apoptosis in NCI‐H929 cells exposed to EB1089 (1 × 10 −7 m for 72 h) using the sub‐G 1 group of the cell cycle by FACS and annexin V binding assays. Induction of apoptosis by EB1089 was associated with down‐regulation of the Bcl‐2 protein without change of the Bax protein. Regarding caspase activity, which plays a crucial role in apoptosis, EB1089‐treated NCI‐H929 cells revealed an increased activity of caspase 3 protease accompanied by degradation of the PARP protein in a dose‐ and time‐dependent manner. In addition, EB1089 caused the down‐regulation of p44 extracellular signal‐related kinase (ERK) activity and up‐regulation of the p38 kinase activity during apoptosis of NCI‐H929 cells. These results suggest that EB1089 inhibits growth of NCI‐H929 cells via G 1 cell cycle arrest as well as apoptosis by activating p38 kinase and suppressing ERK activity.