Surfactin induces apoptosis in human breast cancer MCF-7 cells through a ROS/JNK-mediated mitochondrial/caspase pathway |
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| Authors: | Xiao-hong Cao Ai-hua Wang Chun-ling Wang De-zhi Mao Mei-fang Lu Yun-qian Cui Run-zhi Jiao |
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| Institution: | 1. Departamento de Bioquímica y Biología Molecular-A, Facultad de Veterinaria, Universidad de Murcia, Campus de Espinardo, E-30100 Murcia, Spain;2. Grupo CIBIOP, Departamento de Ingeniería de Procesos, Universidad EAFIT, Carrera 49 No. 7 Sur 50, Medellín, Colombia;1. SN ONGC Department of Genetics and Molecular Biology, Vision Research Foundation, Chennai, 600006, Tamil Nadu, India;2. Human Molecular Cytogenetics and Stem Cell Laboratory, Department of Human Genetics and Molecular Biology, Bharathiar University, Coimbatore, 641046, Tamil Nadu, India;3. Department of Zoology, Avinashilingam Institute for Home Science and Higher Education for Women, Coimbatore, 641 043, Tamil Nadu, India;4. Department of Biotechnology, Mizoram University (A Central University), Aizawl, 796 004, Mizoram, India;5. Farmer''s Bio Fertilizers and Organics, Coimbatore, 641 029, Tamil Nadu, India;6. Department of Biotechnology, Lovely Professional University, Punjab, 144411, India;7. Disease Proteomics Laboratory, Department of Zoology, Bharathiar University, Coimbatore, 641 046, Tamil Nadu, India;8. National Center for Disease Control, Ministry of Health and Family Welfare, Government of India, New Delhi, 110054, India;9. Department of Biomedical Sciences, School of Biosciences and Technology, Vellore Institute of Technology, Vellore, 632 014, Tamil Nadu, India;10. School of Life Sciences, Department of Zoology, Tamil Nadu Open University, Chennai, Tamil Nadu, India;1. Bioengineering and Drug Designing Lab, Department of Biotechnology, Indian Institute of Technology Madras, Chennai 600036, India;2. Metallurgy and Materials Group, Indira Gandhi Centre for Atomic Research, Kalpakkam 603102, Tamil Nadu, India;1. Department of Chemical Engineering, Sri Sivasubramaniya Nadar College of Engineering, Chennai - 603110, India;2. Laboratoire de Chimie Inorganique Appliquée, Faculté des Sciences, Université de Yaoundé I, B.P: 812, Yaoundé, Cameroon |
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| Abstract: | 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. |
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