Surfactin induces apoptosis in human breast cancer MCF-7 cells through a ROS/JNK-mediated mitochondrial/caspase pathway

• Published in: Chemico-biological interactions 2010-02, Vol.183 (3), p.357-362
• Main Authors: Cao, Xiao-hong, Wang, Ai-hua, Wang, Chun-ling, Mao, De-zhi, Lu, Mei-fang, Cui, Yun-qian, Jiao, Run-zhi
• Format: Article
• Language: English
• Subjects: Antibiotics, Antineoplastic - pharmacology; Apoptosis; bcl-2-Associated X Protein - metabolism; bcl-X Protein - metabolism; Breast Neoplasms - enzymology; Breast Neoplasms - metabolism; Caspase 6 - metabolism; Cell Line, Tumor; Cytochromes c - metabolism; Extracellular Signal-Regulated MAP Kinases - metabolism; Female; Humans; JNK Mitogen-Activated Protein Kinases - metabolism; Lipopeptides - pharmacology; MAP Kinase Signaling System; MAPK; Membrane Potential, Mitochondrial - drug effects; Mitochondria; Mitochondria - drug effects; Mitochondria - metabolism; Peptides, Cyclic - pharmacology; Phosphorylation; Reactive Oxygen Species - metabolism; ROS; Surfactin
• ISSN: 0009-2797; 1872-7786
• DOI: 10.1016/j.cbi.2009.11.027

Surfactin has been known to inhibit proliferation and induce apoptosis in cancer cells. However, the molecular mechanisms involved in surfactin-induced apoptosis remain poorly understood. The present study was undertaken to elucidate the underlying network of signaling events in surfactin-induced apoptosis of human breast cancer MCF-7 cells. In this study, surfactin caused reactive oxygen species (ROS) generation and the surfactin-induced cell death was prevented by antioxidants N-acetylcysteine (NAC) and catalase, suggesting involvement of ROS generation in surfactin-induced cell death. Surfactin induced a sustained activation of the phosphorylation of ERK1/2 and JNK, but not p38. Moreover, surfactin-induced cell death was reversed by PD98059 (an inhibitor of ERK1/2) and SP600125 (an inhibitor of JNK), but not by SB203580 (an inhibitor of p38). However, the phosphorylation of JNK rather than ERK1/2 activation by surfactin was blocked by NAC/catalase. These results suggest that the action of surfactin on MCF-7 cells was via ERK1/2 and JNK, but not via p38, and the ERK1/2 and JNK activation induce apoptosis through two independent signaling mechanisms. Surfactin triggered the mitochondrial/caspase apoptotic pathway indicated by enhanced Bax-to-Bcl-2 expression ratio, loss of mitochondrial membrane potential, cytochrome c release, and caspase cascade reaction. The NAC and SP600125 blocked these events induced by surfactin. Moreover, the general caspase inhibitor z-VAD-FMK inhibited the caspase-6 activity and exerted the protective effect against the surfactin-induced cell death. Taken together, these findings suggest that the surfactin induces apoptosis through a ROS/JNK-mediated mitochondrial/caspase pathway.