<?xml version='1.0' encoding='UTF-8'?><xml><records><record><source-app name="HighWire" version="7.x">Drupal-HighWire</source-app><ref-type name="Journal Article">17</ref-type><contributors><authors><author><style face="normal" font="default" size="100%">MORINAGA, SEI</style></author><author><style face="normal" font="default" size="100%">HAN, QINGHONG</style></author><author><style face="normal" font="default" size="100%">MIZUTA, KOHEI</style></author><author><style face="normal" font="default" size="100%">KANG, BYUNG MO</style></author><author><style face="normal" font="default" size="100%">SATO, MOTOKAZU</style></author><author><style face="normal" font="default" size="100%">BOUVET, MICHAEL</style></author><author><style face="normal" font="default" size="100%">YAMAMOTO, NORIO</style></author><author><style face="normal" font="default" size="100%">HAYASHI, KATSUHIRO</style></author><author><style face="normal" font="default" size="100%">KIMURA, HIROAKI</style></author><author><style face="normal" font="default" size="100%">MIWA, SHINJI</style></author><author><style face="normal" font="default" size="100%">IGARASHI, KENTARO</style></author><author><style face="normal" font="default" size="100%">HIGUCHI, TAKASHI</style></author><author><style face="normal" font="default" size="100%">TSUCHIYA, HIROYUKI</style></author><author><style face="normal" font="default" size="100%">DEMURA, SATORU</style></author><author><style face="normal" font="default" size="100%">HOFFMAN, ROBERT M.</style></author></authors><secondary-authors></secondary-authors></contributors><titles><title><style face="normal" font="default" size="100%">Extensive DNA Damage and Loss of Cell Viability Occur Synergistically With the Combination of Recombinant Methioninase and Paclitaxel on Pancreatic Cancer Cells which Report DNA-Damage Response in Real Time</style></title><secondary-title><style face="normal" font="default" size="100%">Cancer Genomics - Proteomics</style></secondary-title></titles><dates><year><style  face="normal" font="default" size="100%">2024</style></year><pub-dates><date><style  face="normal" font="default" size="100%">2024-11-01 00:00:00</style></date></pub-dates></dates><pages><style  face="normal" font="default" size="100%">585-590</style></pages><doi><style  face="normal" font="default" size="100%">10.21873/cgp.20475</style></doi><volume><style face="normal" font="default" size="100%">21</style></volume><issue><style face="normal" font="default" size="100%">6</style></issue><abstract><style  face="normal" font="default" size="100%">Background/Aim: Methionine restriction selectively arrests cancer cells during the S-phase of the cell cycle. We hypothesized that DNA damage may occur in S-phase in cancer cells during methionine restriction. To determine if this occurs, we used MiaPaCa-2Tet-On 53BP1-green fluorescent protein (GFP) pancreatic cancer cells, which report GFP fluorescence in real time after DNA-damage response (DDR) in these cells. We also determined whether a chemotherapy drug in combination with methionine restriction increases the rate of DNA damage. Materials and Methods: MiaPaCa-2Tet-On 53BP1-GFP cells were used for in vitro experiments. The 25% and 50% inhibitory concentrations (IC25 and IC50, respectively) of recombinant methioninase (rMETase) and paclitaxel on MiaPaCa-2Tet-On 53BP1-GFP pancreatic cancer cells were determined. Cell viability and DDR with rMETase alone, paclitaxel alone, and their combination were measured in MiaPaCa-2Tet-On 53BP1-GFP cells. Results: The IC25 of rMETase on MiaPaCa-2Tet-On 53BP1-GFP cells was 1.66 U/ml. The IC25 for paclitaxel on MiaPaCa-2Tet-On 53BP1-GFP cells was 3.31 nM. The combination of rMETase and paclitaxel synergistically reduced the viability of MiaPaCa-2Tet-On 53BP1-GFP cells. The IC50 of paclitacel on MiaPaCa-2Tet-On 53BP1-GFP cells was 5.1 nM. The IC50 of rMETase on MiaPaCa-2Tet-On 53BP1-GFP cells was 2.3 U/ml. The combination of rMETase (IC50) plus paclitaxel (IC50) on MiaPaCa-2Tet-On 53BP1-GFP cells also caused more DNA damage than either agent alone. Conclusion: The present study suggests the synergy of methionine restriction and chemotherapy is due, at least in part, to DNA damage of cancer cells.</style></abstract></record></records></xml>