Shengmai Formula suppressed over-activated Ras/MAPK pathway in C. elegans by opening mitochondrial permeability transition pore via regulating cyclophilin D
作者： Yan Liu , Dejuan Zhi , Menghui Li , Dongling Liu , Xin Wang
DOI: 10.1038/SREP38934
关键词: Apoptosis 、 Biology 、 Mitochondrial permeability transition pore 、 p38 mitogen-activated protein kinases 、 MAPK/ERK pathway 、 Anti-apoptotic Ras signalling cascade 、 Signal transduction 、 Cell biology 、 Oncogene Protein p21(ras) 、 Mitochondrial membrane transport protein
摘要: Since about 30% of all human cancers contain mutationally activated Ras, down regulating the over-activation Ras/MAPK pathway represents a viable approach for treating cancers. Over-activation is accompanied by accumulation reactive oxygen species (ROS). One developing anti-cancer drugs to target ROS production and their accumulation. To test this idea, we have employed C. elegans let-60 (gf) mutant, which over-activated (the homolog mammalian ras) exhibit tumor-like symptom multivulva phenotype, determine whether anti-oxidants can affect phenotype. Specifically studied effect Shengmai formula (SM), traditional Chinese medicine that has strong anti-oxidant activity, on physiology mutants. Unexpectedly, found SM treatment led opening mitochondrial permeability transition pore cyclophilin D then triggered oxidative stress related signaling activation, including p53, JNK, p38/MAPK pathways. Finally, induced apoptosis inhibited phenotype let-60(gf) Our results provide evidences support act as pro-oxidant agent could serve potential drug candidate combating Ras-related cancer.
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