Induction of apoptosis by streptochlorin isolated from Streptomyces sp. in human leukemic U937 cells.
Streptochlorin is a small molecule that produced by marine Streptomyces sp. that is known to have anti-angiogenic and anti-cancer properties. However, the mechanism by which streptochlorin functions is not well understood. In this study, we investigated the pro-apoptotic effect of streptochlorin in human leukemic U937 cells. Streptochlorin treatment resulted in concentration- and time-dependent growth inhibition by inducing apoptosis. The increase in apoptosis that was induced by streptochlorin was correlated with down-regulation of anti-apoptotic Bcl-2 expression, up-regulation of pro-apoptotic Bax and FasL, a decrease in the mitochondrial membrane potential (MMP), activation of caspases and degradation of poly-(ADP-ribose)polymerase and phospholipase C-gamma1 protein. In addition, the cytotoxic effects and apoptotic characteristics induced by streptochlorin were significantly inhibited by z-DEVD-fmk, a caspase-3 inhibitor, which demonstrates the important role that caspase-3 played in the process. Furthermore, Bcl-2 overexpression significantly reversed the streptochlorin-induced growth inhibitory effects via inhibition of the MMP collapse and caspases activation and effectively attenuated the apoptotic response to streptochlorin. However, the elevated levels of FasL expression induced by streptochlorin were not reduced by Bcl-2 overexpression. Taken together, these findings demonstrate that the pro-apoptotic effect of streptochlorin is mediated through activation of caspases and mitochondria in U937 cells.
Park
Cheol
C
Department of Biochemistry, Dongeui University College of Oriental Medicine, Department of Biomaterial Control (BK21 Program), Dongeui University Graduate School, Yangjung-dong San 45, Busanjin-gu, Busan, South Korea.
Shin
Hee Jae
HJ
Kim
Gi-Young
GY
Kwon
Taeg Kyu
TK
Nam
Taek-Jeong
TJ
Kim
Se-Kwon
SK
Cheong
Jaehun
J
Choi
Il-Whan
IW
Choi
Yung Hyun
YH
D017209:Apoptosis / Q000187:drug effects*; D053148:Caspase 3 / Q000187:drug effects / Q000378:metabolism; D020169:Caspases / Q000187:drug effects / Q000378:metabolism; D053222:Fas Ligand Protein / Q000187:drug effects / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D007211:Indoles / Q000008:administration & dosage / Q000302:isolation & purification / Q000494:pharmacology*; D007938:Leukemia / Q000378:metabolism*; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D010080:Oxazoles / Q000008:administration & dosage / Q000302:isolation & purification / Q000494:pharmacology*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000187:drug effects / Q000378:metabolism; D013302:Streptomyces / Q000737:chemistry*; D013997:Time Factors; D020298:U937 Cells
D053222:Fas Ligand Protein; D007211:Indoles; D010080:Oxazoles; D019253:Proto-Oncogene Proteins c-bcl-2; C526070:streptochlorin; D053148:Caspase 3; D020169:Caspases