ROS-Ca(2+) is associated with mitochondria permeability transition pore involved in surfactin-induced MCF-7 cells apoptosis.
The surfactin can inhibit proliferation and induce apoptosis in cancer cells. Moreover, surfactin can induce cell death in human breast cancer MCF-7 cells through mitochondrial pathway. However, the molecular mechanism involved in this pathway remains to be elucidated. Here, the reactive oxygen species (ROS) and Ca(2+) on mitochondria permeability transition pore (MPTP) activity, and MCF-7 cell apoptosis which induced by surfactin were investigated. It is found that surfactin evoked mitochondrial ROS generation, and the surfactin-induced cell death was prevented by N-acetylcysteine (NAC, an inhibitor of ROS). An increasing cytoplasmic Ca(2+) concentration was detected in surfactin-induced MCF-7 apoptosis, which was inhibited by 1,2-bis (2-aminophenoxy) ethane-N,N,N',N'-tetraacetic acid (BAPTA-AM, a chelator of calcium). In addition, the relationship between ROS generation and the increase of cytoplasm Ca(2+) was determined. The results showed that surfactin initially induced the ROS formation, leading to the MPTP opening accompanied with the collapse of mitochondrial membrane potential (ΔΨ(m)). Then the cytoplasmic Ca(2+) concentration increased in virtue of the changes of mitochondrial permeability, which was prevented by BAPTA-AM. Besides, cytochrome c (cyt c) was released from mitochondria to cytoplasm through the MPTP and activated caspase-9, eventually induced apoptosis. In summary, surfactin has notable anti-tumor effect on MCF-7 cells, however, there was no obvious cytotoxicity on normal cells.
Key Laboratory of Food Nutrition and Safety (Tianjin University of Science & Technology), Ministry of Education, China.
Xiao-Hong
XH
Cao
Si-Si
SS
Zhao
Dong-Yue
DY
Liu
Zhuo
Z
Wang
Li-Li
LL
Niu
Li-Hua
LH
Hou
Chun-Ling
CL
Wang
D000111:Acetylcysteine / Q000494:pharmacology; D017209:Apoptosis; D002118:Calcium / Q000378:metabolism*; D053453:Caspase 9 / Q000378:metabolism; D045744:Cell Line, Tumor; D002463:Cell Membrane Permeability; D049109:Cell Proliferation; D045304:Cytochromes c / Q000378:metabolism; D004533:Egtazic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D006801:Humans; D055666:Lipopeptides / Q000494:pharmacology*; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D008928:Mitochondria / Q000187:drug effects* / Q000378:metabolism; D010456:Peptides, Cyclic / Q000494:pharmacology*; D017382:Reactive Oxygen Species / Q000378:metabolism*
D055666:Lipopeptides; D010456:Peptides, Cyclic; D017382:Reactive Oxygen Species; C070379:1,2-bis(2-aminophenoxy)ethane N,N,N',N'-tetraacetic acid acetoxymethyl ester; C009365:surfactin peptide; D004533:Egtazic Acid; D045304:Cytochromes c; D053453:Caspase 9; D002118:Calcium; D000111:Acetylcysteine