Apoptotic mechanism of WJH-6, a novel polyamine conjugate, on K562 and HL-60 cells.
- Author:
Songqiang XIE
;
Qian LI
;
Hongxia MA
;
Yahong ZHANG
;
Jianhong WANG
;
Jin ZHAO
;
Chaojie WANG
- Publication Type:Journal Article
- From:
Acta Pharmaceutica Sinica
2010;45(4):451-5
- 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.