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10.1038/s41419-018-0641-7 http://scihub22266oqcxt.onion/10.1038/s41419-018-0641-7 C5964100!5964100 !29789524     free     free     free Warning: file_get_contents(https://eutils.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&id=29789524 &cmd=llinks): Failed to open stream: HTTP request failed! 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Hirsutine induces mPTP-dependent apoptosis through ROCK1/PTEN/PI3K/GSK3? pathway in human lung cancer cells |pdf=|usr=}}{{29789524 }} gab.com Text Hirsutine induces mPTP-dependent apoptosis through ROCK1/PTEN/PI3K/GSK3 pathway in human lung cancer cells JO: Cell Death Dis http://www.kidney.de/pget.php?&tw=1&pmid=29789524 #FOAvip Hirsutine extracted from Uncaria rhynchophylla has been shown to exhibit anti-cancer activity. However, the molecular mechanism by which hirsutine exhibits anti-lung cancer activity remains unclear. In the present study, we showed that hirsutine induces apoptosis in human lung cancer cells via loss of mitochondrial membrane potential (??m), adenosine triphosphate (ATP) depletion, ROS production, as well as cytochrome c release. Dephosphorylation of GSK3? is involved in hirsutine-mediated mitochondrial permeability transition pore (mPTP) opening through ANT1/CypD interaction. Mechanistic study revealed that interruption of ROCK1/PTEN/PI3K/Akt signaling pathway plays a critical role in hirsutine-mediated GSK3? dephosphorylation and mitochondrial apoptosis. Our in vivo study also showed that hirsutine effectively inhibits tumor growth in a A549 xenograft mouse model through ROCK1/PTEN/PI3K/Akt signaling-mediated GSK3? dephosphorylation and apoptosis. Collectively, these findings suggest a hierarchical model in which induction of apoptosis by hirsutine stems primarily from activation of ROCK1 and PTEN, inactivation of PI3K/Akt, leading in turn to GSK3? dephosphorylation and mPTP opening, and culminating in caspase-3 activation and apoptosis. These findings could provide a novel mechanistic basis for the application of hirsutine in the treatment of human lung cancer. Twit Text FOAVip Hirsutine induces mPTP-dependent apoptosis through ROCK1/PTEN/PI3K/GSK3 pathway in human lung cancer cells ????Cell Death Dis http://www.kidney.de/pget.php?&tw=1&pmid=29789524 #FOAvip Twit Text # Free Paper on # # # # # LINK http://www.kidney.de/pget.php?&tw=1&pmid=29789524 #FOAvip English Wikipedia <ref>{{Cite pmid|29789524 }}</ref> Hirsutine induces mPTP-dependent apoptosis through ROCK1/PTEN/PI3K/GSK3? pathway in human lung cancer cells #MMPMID29789524 Zhang R ; Li G ; Zhang Q ; Tang Q ; Huang J ; Hu C ; Liu Y ; Wang Q ; Liu W ; Gao N ; Zhou S Cell Death Dis 2018[May]; 9 (6 ): 598 PMID29789524 show ga Hirsutine extracted from Uncaria rhynchophylla has been shown to exhibit anti-cancer activity. However, the molecular mechanism by which hirsutine exhibits anti-lung cancer activity remains unclear. In the present study, we showed that hirsutine induces apoptosis in human lung cancer cells via loss of mitochondrial membrane potential (??m), adenosine triphosphate (ATP) depletion, ROS production, as well as cytochrome c release. Dephosphorylation of GSK3? is involved in hirsutine-mediated mitochondrial permeability transition pore (mPTP) opening through ANT1/CypD interaction. Mechanistic study revealed that interruption of ROCK1/PTEN/PI3K/Akt signaling pathway plays a critical role in hirsutine-mediated GSK3? dephosphorylation and mitochondrial apoptosis. Our in vivo study also showed that hirsutine effectively inhibits tumor growth in a A549 xenograft mouse model through ROCK1/PTEN/PI3K/Akt signaling-mediated GSK3? dephosphorylation and apoptosis. Collectively, these findings suggest a hierarchical model in which induction of apoptosis by hirsutine stems primarily from activation of ROCK1 and PTEN, inactivation of PI3K/Akt, leading in turn to GSK3? dephosphorylation and mPTP opening, and culminating in caspase-3 activation and apoptosis. These findings could provide a novel mechanistic basis for the application of hirsutine in the treatment of human lung cancer. |*Signal Transduction [MESH] |A549 Cells [MESH] |Adenine Nucleotide Translocator 1/metabolism [MESH] |Adenosine Triphosphate/metabolism [MESH] |Alkaloids/chemistry/*pharmacology [MESH] |Animals [MESH] |Apoptosis/*drug effects [MESH] |Cell Proliferation/drug effects [MESH] |Cyclophilins/metabolism [MESH] |Cytochromes c/metabolism [MESH] |Glycogen Synthase Kinase 3 beta/metabolism [MESH] |Humans [MESH] |Lung Neoplasms/metabolism/*pathology/ultrastructure [MESH] |Membrane Potential, Mitochondrial/drug effects [MESH] |Mice, Nude [MESH] |Mitochondria/drug effects/metabolism/ultrastructure [MESH] |Mitochondrial Membrane Transport Proteins/*metabolism [MESH] |Mitochondrial Permeability Transition Pore [MESH] |Models, Biological [MESH] |PTEN Phosphohydrolase/metabolism [MESH] |Peptidyl-Prolyl Isomerase F [MESH] |Phosphatidylinositol 3-Kinases/metabolism [MESH] |Phosphorylation/drug effects [MESH] |Reactive Oxygen Species/metabolism [MESH] |Xenograft Model Antitumor Assays [MESH]Hirsutine induces mPTP-dependent apoptosis through ROCK1/PTEN/PI3K/GSK(epmc).pdf DeepDyve Pubget Overpricing