Streptochlorin isolated from Streptomyces sp. Induces apoptosis in human hepatocarcinoma cells through a reactive oxygen species-mediated mitochondrial pathway.
Streptochlorin is a small molecule isolated from marine Streptomyces sp. that is known to have antiangiogenic and anticancer properties. In this study, we examined the effects of this compound on reactive oxygen species (ROS) production and the association of these effects with apoptotic tumor cell death, using a human hepatocarcinoma Hep3B cell line. The results of this study demonstrated that streptochlorin mediates ROS production, and that this mediation is followed by a decrease in the mitochondrial membrane potential (MMP, m), activation of caspase-3, and downregulation of antiapoptotic Bcl-2 protein. The quenching of ROS generation by N-acetyl-L-cysteine administration, a scavenger of ROS, reversed the streptochlorin-induced apoptosis effects via inhibition of ROS production, MMP collapse, and the subsequent activation of caspase-3. These observations clearly indicate that ROS are involved in the early molecular events in the streptochlorin-induced apoptotic pathway. Taken together, our data imply that streptochlorin-induced ROS is a key mediator of MMP collapse, which leads to the caspase-3 activation, culminating in apoptosis.
Shin
Dong Yeok
DY
Department of Biochemistry, Dongeui University College of Oriental Medicine and Department of Biomaterial Control (BK21Program), Dongeui University Graduate School, Busan 614-052, Korea.
Shin
Hee Jae
HJ
Kim
Gi-Young
GY
Cheong
Jaehun
J
Choi
Il-Whan
IW
Kim
Se-Kwon
SK
Moon
Sung-Kwon
SK
Kang
Ho Sung
HS
Choi
Yung Hyun
YH
D017209:Apoptosis / Q000187:drug effects; D006528:Carcinoma, Hepatocellular; D045744:Cell Line, Tumor; D006801:Humans; D007211:Indoles / Q000302:isolation & purification / Q000378:metabolism / Q000494:pharmacology*; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects / Q000502:physiology; D008928:Mitochondria / Q000378:metabolism* / Q000502:physiology; D010080:Oxazoles / Q000302:isolation & purification / Q000378:metabolism / Q000494:pharmacology*; D017382:Reactive Oxygen Species / Q000378:metabolism* / Q000494:pharmacology; D013302:Streptomyces / Q000378:metabolism*
D007211:Indoles; D010080:Oxazoles; D017382:Reactive Oxygen Species; C526070:streptochlorin