Apoptotic mechanism of WJH-6, a novel polyamine conjugate, on K562 and HL-60 cells.
- Author:
Song-qiang XIE
1
;
Qian LI
;
Hong-xia MA
;
Ya-hong ZHANG
;
Jian-hong WANG
;
Jin ZHAO
;
Chao-jie WANG
Author Information
1. Institute of Chemistry & Biology, Henan University, Kaifeng 475004, China. wcjsxq@henu.edu.cn
- Publication Type:Journal Article
- MeSH:
Antineoplastic Agents;
pharmacology;
Apoptosis;
drug effects;
BH3 Interacting Domain Death Agonist Protein;
metabolism;
Caspase 3;
metabolism;
Caspase 8;
metabolism;
Caspase 9;
metabolism;
Cell Cycle;
drug effects;
Cell Proliferation;
drug effects;
Cytochromes c;
metabolism;
Cytoplasm;
metabolism;
Enzyme Activation;
drug effects;
HL-60 Cells;
Humans;
K562 Cells;
Membrane Potential, Mitochondrial;
drug effects;
Mitochondria;
metabolism;
Polyamines;
pharmacology
- From:
Acta Pharmaceutica Sinica
2010;45(4):451-455
- CountryChina
- Language:Chinese
-
Abstract:
In the present study, the apoptotic mechanism and polyamine transporter recognition of WJH-6, a novel polyamine conjugate, were investigated in K562 and HL-60 cells. The cytotoxicity of WJH-6 was assessed by MTT assay; cell cycle distribution and apoptosis were measured by flow cytometry; the protein expression of Caspase-3, Caspase-8, Caspase-9, Bid and mitochondrial membrane potential (MMP) were evaluated by high content screening (HCS) analysis; the protein expression of cytochrome c was measured by Western blotting. The results showed that WJH-6 could be recognized and transported by polyamine transporter (PAT). Furthermore, WJH-6 was able to inhibit K562 and HL-60 cells proliferation and induce apoptosis. This apoptotic effect was relative to MMP loss, cytochrome c release from mitochondria to cytoplasm and the activation of Caspase-8, Caspase-9, Caspase-3 and Bid. These results suggested that WJH-6-induced K562 and HL-60 cells apoptosis was related with mitochondrial damage.