Pub. Date : 2018 Jul 20
PMID : 30029680
16 Functional Relationships(s)Download |
Sentence | Compound Name | Protein Name | Organism |
| 1 | Regulation of tNOX expression through the ROS-p53-POU3F2 axis contributes to cellular responses against oxaliplatin in human colon cancer cells. | Oxaliplatin | tumor protein p53 | Homo sapiens |
| 2 | We recently established that oxaliplatin also exert its anti-cancer activity in gastric cancer cell lines by targeting tumor-associated NADH oxidase (tNOX), attenuate NAD+ generation and reduce NAD+-dependent sirtuin 1 (SIRT1) deacetylase activity, which in turn enhances p53 acetylation and apoptosis. | Oxaliplatin | tumor protein p53 | Homo sapiens |
| 3 | METHODS: In this study, differential cellular outcomes in response to oxaliplatin exposure of p53-wild-type versus p53-null HCT116 human colon cancer cells were examined. | Oxaliplatin | tumor protein p53 | Homo sapiens |
| 4 | METHODS: In this study, differential cellular outcomes in response to oxaliplatin exposure of p53-wild-type versus p53-null HCT116 human colon cancer cells were examined. | Oxaliplatin | tumor protein p53 | Homo sapiens |
| 5 | RESULTS: In p53-wild-type cells, we found that oxaliplatin inhibited cell growth by inducing apoptosis and concurrently down-regulating tNOX at both the transcriptional and translational levels. | Oxaliplatin | tumor protein p53 | Homo sapiens |
| 6 | In p53-null cells, in contrast, oxaliplatin moderately up-regulated tNOX expression and yielded no apoptosis and much less cytotoxicity. | Oxaliplatin | tumor protein p53 | Homo sapiens |
| 7 | Further experiments revealed that in p53-wild-type cells, oxaliplatin enhanced ROS generation and p53 transcriptional activation, leading to down-regulation of the transcriptional factor, POU3F2, which enhances the expression of tNOX. | Oxaliplatin | tumor protein p53 | Homo sapiens |
| 8 | Further experiments revealed that in p53-wild-type cells, oxaliplatin enhanced ROS generation and p53 transcriptional activation, leading to down-regulation of the transcriptional factor, POU3F2, which enhances the expression of tNOX. | Oxaliplatin | tumor protein p53 | Homo sapiens |
| 9 | Moreover, the addition of a ROS scavenger reversed the p53 activation, POU3F2 down-regulation, and apoptosis induced by oxaliplatin in p53-wild-type cells. | Oxaliplatin | tumor protein p53 | Homo sapiens |
| 10 | Moreover, the addition of a ROS scavenger reversed the p53 activation, POU3F2 down-regulation, and apoptosis induced by oxaliplatin in p53-wild-type cells. | Oxaliplatin | tumor protein p53 | Homo sapiens |
| 11 | In the p53-null line, on the other hand, oxaliplatin treatment triggered less ROS generation and no p53 protein, such that POU3F2 and tNOX were not down-regulated and oxaliplatin-mediated cytotoxicity was attenuated. | Oxaliplatin | tumor protein p53 | Homo sapiens |
| 12 | In the p53-null line, on the other hand, oxaliplatin treatment triggered less ROS generation and no p53 protein, such that POU3F2 and tNOX were not down-regulated and oxaliplatin-mediated cytotoxicity was attenuated. | Oxaliplatin | tumor protein p53 | Homo sapiens |
| 13 | In the p53-null line, on the other hand, oxaliplatin treatment triggered less ROS generation and no p53 protein, such that POU3F2 and tNOX were not down-regulated and oxaliplatin-mediated cytotoxicity was attenuated. | Oxaliplatin | tumor protein p53 | Homo sapiens |
| 14 | CONCLUSION: Our results show that oxaliplatin mediates differential cellular responses in colon cancer cells depending on their p53 status, and demonstrate that the ROS-p53 axis is important for regulating POU3F2 and its downstream target, tNOX. | Oxaliplatin | tumor protein p53 | Homo sapiens |
| 15 | CONCLUSION: Our results show that oxaliplatin mediates differential cellular responses in colon cancer cells depending on their p53 status, and demonstrate that the ROS-p53 axis is important for regulating POU3F2 and its downstream target, tNOX. | Oxaliplatin | tumor protein p53 | Homo sapiens |
| 16 | Notably, the depletion of tNOX sensitizes p53-null cells to both spontaneous and oxaliplatin-induced apoptosis. | Oxaliplatin | tumor protein p53 | Homo sapiens |