[Inducement effect of (DIPP-L-Trp)2-L-Lys-OCH3 on apoptosis of K562 cells through mitochondrial-dependent pathway].
OBJECTIVE
Phosphorylation of protein and peptide plays an important role in life activity. Some phosphoryl peptides are found to have activities to inhibit proliferation of tumor cells, but the involved mechanisms are unclear. This study was designed to investigate cell apoptosis induced by (O,O-diisopropyl phosphoryl-L-tryptophan)(2)-L-lysine methyl ester [(DIPP-L-Trp)(2)-L-Lys-OCH(3)], and its mechanism in K562 cells.


METHODS
K562 cells were double stained by AnnexinV-FITC and propidium iodide (PI) to detect (DIPP-L-Trp)(2)-L-Lys-OCH(3)-induced apoptosis by flow cytometry (FCM). After treatment of different concentrations of (DIPP-L-Trp)(2)-L-Lys-OCH(3), K562 cells were stained by rhodamine123 and PI to detect changes in membrane potential (Delta Psi m), or stained by 2',7'-dichlorofluorescein diacetate (DCFH-DA) to detect reactive oxygen species (ROS) of mitochondrial by FCM.


RESULTS
When treated with 50 microg/ml of (DIPP-L-Trp)(2)-L-Lys-OCH(3) for 24 h, apoptosis rate of K562 cells was 61.9%, Delta Psi m was decreased in 93.6% of K562 cells,and ROS production was decreased. Both Delta Psi m and ROS production in K562 cells mitochondria were decreased with the increasing concentration and extending treatment time of (DIPP-L-Trp)(2)-L-Lys-OCH(3).


CONCLUSIONS
(DIPP-L-Trp) (2)-L-Lys-OCH(2) could induce apoptosis in K562 cells, which might relate with down-regulation of mitochondrial Delta Psi m and reduction of ROS production.
Liu
Feng
F
Department of Biological Sciences and Biotechnology, Tsinghua University, Beijing, 100084, P. R. China.
Jiang
Yu-Yang
YY
Liu
Shi-Ying
SY
Wang
Kai
K
Cao
Jian
J
Zhao
Yu-Fen
YF
D017209:Apoptosis / Q000187:drug effects*; D004151:Dipeptides / Q000008:administration & dosage / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation; D006801:Humans; D020014:K562 Cells; D008564:Membrane Potentials / Q000187:drug effects; D008928:Mitochondria / Q000378:metabolism / Q000502:physiology*; D017382:Reactive Oxygen Species / Q000378:metabolism*
C511841:(O,O-diisopropyl phosphoryl-L-tryptophan)(2)-L-lysine methyl ester; D004151:Dipeptides; D017382:Reactive Oxygen Species