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10.1371/journal.pone.0185141 http://scihub22266oqcxt.onion/10.1371/journal.pone.0185141 C5605006!5605006 !28926637     free     free     free Warning: file_get_contents(https://eutils.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&id=28926637 &cmd=llinks): Failed to open stream: HTTP request failed! 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Selective cytotoxicity of the anti-diabetic drug, metformin, in glucose-deprived chicken DT40 cells |pdf=|usr=}}{{28926637 }} gab.com Text Selective cytotoxicity of the anti-diabetic drug, metformin, in glucose-deprived chicken DT40 cells JO: PLoS One http://www.kidney.de/pget.php?&tw=1&pmid=28926637 #FOAvip Metformin is a biguanide drug that is widely used in the treatment of diabetes. Epidemiological studies have indicated that metformin exhibits anti-cancer activity. However, the molecular mechanisms underlying this activity currently remain unclear. We hypothesized that metformin is cytotoxic in a tumor-specific environment such as glucose deprivation and/or low oxygen (O2) tension. We herein demonstrated that metformin was highly cytotoxic under glucose-depleted, but not hypoxic (2% O2) conditions. In order to elucidate the underlying mechanisms of this selective cytotoxicity, we treated exposed DNA repair-deficient chicken DT40 cells with metformin under glucose-depleted conditions and measured cellular sensitivity. Under glucose-depleted conditions, metformin specifically killed fancc and fancl cells that were deficient in FANCC and FANCL proteins, respectively, which are involved in DNA interstrand cross-link repair. An analysis of chromosomal aberrations in mitotic chromosome spreads revealed that a clinically relevant concentration of metformin induced DNA double-strand breaks (DSBs) in fancc and fancl cells under glucose-depleted conditions. In summary, metformin induced DNA damage under glucose-depleted conditions and selectively killed cells. This metformin-mediated selective toxicity may suppress the growth of malignant tumors that are intrinsically deprived of glucose. Twit Text FOAVip Selective cytotoxicity of the anti-diabetic drug, metformin, in glucose-deprived chicken DT40 cells ????PLoS One http://www.kidney.de/pget.php?&tw=1&pmid=28926637 #FOAvip Twit Text # Free Paper on # # # # # LINK http://www.kidney.de/pget.php?&tw=1&pmid=28926637 #FOAvip English Wikipedia <ref>{{Cite pmid|28926637 }}</ref> Selective cytotoxicity of the anti-diabetic drug, metformin, in glucose-deprived chicken DT40 cells #MMPMID28926637 Kadoda K ; Moriwaki T ; Tsuda M ; Sasanuma H ; Ishiai M ; Takata M ; Ide H ; Masunaga SI ; Takeda S ; Tano K PLoS One 2017[]; 12 (9 ): e0185141 PMID28926637 show ga Metformin is a biguanide drug that is widely used in the treatment of diabetes. Epidemiological studies have indicated that metformin exhibits anti-cancer activity. However, the molecular mechanisms underlying this activity currently remain unclear. We hypothesized that metformin is cytotoxic in a tumor-specific environment such as glucose deprivation and/or low oxygen (O2) tension. We herein demonstrated that metformin was highly cytotoxic under glucose-depleted, but not hypoxic (2% O2) conditions. In order to elucidate the underlying mechanisms of this selective cytotoxicity, we treated exposed DNA repair-deficient chicken DT40 cells with metformin under glucose-depleted conditions and measured cellular sensitivity. Under glucose-depleted conditions, metformin specifically killed fancc and fancl cells that were deficient in FANCC and FANCL proteins, respectively, which are involved in DNA interstrand cross-link repair. An analysis of chromosomal aberrations in mitotic chromosome spreads revealed that a clinically relevant concentration of metformin induced DNA double-strand breaks (DSBs) in fancc and fancl cells under glucose-depleted conditions. In summary, metformin induced DNA damage under glucose-depleted conditions and selectively killed cells. This metformin-mediated selective toxicity may suppress the growth of malignant tumors that are intrinsically deprived of glucose. |Animals [MESH] |Cell Line [MESH] |Cell Survival/drug effects [MESH] |Chickens [MESH] |Chromosome Aberrations/drug effects [MESH] |DNA Breaks, Double-Stranded/*drug effects [MESH] |DNA Repair/drug effects [MESH] |Glucose/chemistry [MESH] |Hypoglycemic Agents/*toxicity [MESH] |Metformin/*toxicity [MESH]Selective cytotoxicity of the anti-diabetic drug, metformin, in glucos(epmc).pdf DeepDyve Pubget Overpricing