GAD 67KD antisense in colon cancer cells inhibits cell growth and sensitizes to butyrate and pH reduction and H2O2 and gamma-radiation.
In eukaryotes, glutamate decarboxylase (GAD) expression was found in brain, kidney, and several kinds of tumor tissues. But its function has been emphasized only as a neurotransmitter-synthesizer, the role in controlling intracellular physiology is poorly understood. According to our studies, when GAD 67KD expression in colon cancer HT-29 cell was repressed by antisense DNA, the cell proliferation was significantly inhibited. GAD 67KD antisensed cells exhibited the low glutathione and high reactive oxygen species level. More importantly, these cells were extremely sensitive to butyrate or pH reduction, both of which naturally cause metabolic stress in the colon lumen, as well as H2O2 and ionizing radiation. These data indicate that GAD 67KD regulates the intracellular redox potential and is important for resistance to acidic or oxidative stress. So, based on these results, we suggest that inhibition of GAD 67KD expression has potentially important implications for overcoming the drug resistance of cancer cells.
Moon
Myung Sook
MS
Department of Radiation Biology, Environmental Radiation Research Group, Korea Atomic Energy Research Institute, PO Box 105, Yusong, Taejon 305-600, Republic of Korea.
Cho
Eun Wie
EW
Byun
Hee Sun
HS
Jung
Il Lae
IL
Kim
In Gyu
IG
D002087:Butyrates / Q000494:pharmacology*; D016923:Cell Death / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects*; D003110:Colonic Neoplasms / Q000378:metabolism* / Q000473:pathology; D005720:Gamma Rays; D005968:Glutamate Decarboxylase / Q000378:metabolism*; D005978:Glutathione / Q000032:analysis / Q000378:metabolism; D019073:HT29 Cells; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology*; D006863:Hydrogen-Ion Concentration; D016376:Oligonucleotides, Antisense / Q000494:pharmacology*; D011838:Radiation-Sensitizing Agents / Q000627:therapeutic use; D017382:Reactive Oxygen Species / Q000378:metabolism
D002087:Butyrates; D016376:Oligonucleotides, Antisense; D011838:Radiation-Sensitizing Agents; D017382:Reactive Oxygen Species; D006861:Hydrogen Peroxide; D005968:Glutamate Decarboxylase; D005978:Glutathione