ROS-Ca is associated with mitochondria permeability transition pore involved in surfactin-induced MCF-7 cells apoptosis |
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Authors: | Xiao-hong Cao Si-si Zhao Dong-yue Liu Zhuo Wang Li-li Niu Li-hua Hou Chun-ling Wang |
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Affiliation: | Key Laboratory of Food Nutrition and Safety (Tianjin University of Science & Technology), Ministry of Education, China |
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Abstract: | 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 Ca2+ 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 Ca2+ 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 Ca2+ 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 (ΔΨm). Then the cytoplasmic Ca2+ 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. |
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Keywords: | Abbreviations: MPTP, mitochondria permeability transition pore VDAC, voltage-dependent anion channel ANT, adenine nucleotide transporter CyP-D, cyclophilin D ATP, adenosine triphosphate ADP, adenosine diphosphate CsA, cyclosporin A ΔΨm, mitochondrial membrane potential cyt c, cytochrome c ROS, reactive oxygen species NAC, N-acetylcysteine BAPTA-AM, 1,2-bis (2-aminophenoxy) ethane-N,N,N&prime ,N&prime -tetraacetic acid DCFH-DA, 2&prime 7&prime -dichlorofluorescein diacetate calcein-AM, calcein acetoxymethyl ester PBS, phosphate-buffered saline [Ca2+]c, cytoplasmic calcium concentration LSCM, laser scanning confocal microscope FCM, flow cytometry |
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