Up-regulation of telomere-binding TRF1, TRF2 related to reactive oxygen species induced by As(2)O(3) in MGC-803 cells.
In this work, our study focused on As(2)O(3) action in view point of telomere. Results showed that treatment of human gastric cancer MGC-803 cells with arsenic trioxide could cause up-regulation of telomeric repeat binding factor TRF1 and TRF2 mRNA and protein levels, and induced G2/M phase arrest and cell apoptosis. At the same time, telomere length shortening and telomerase inhibitory were not obvious. Flow cytometry measurements indicated that the increase of TRF1 and TRF2 proteins is related to oxidative stress by arsenic trioxide. Results also indicate that after arsenic trioxide treatment, p53 protein levels increased significantly and also could bind directly at the telomere t-loop junction. These findings demonstrate arsenic trioxide-induced cell cycle arrest and apoptosis might involve a novel pathway related to TRF1, TRF2 protein.
Zhang
Yan
Y
Institute of Biophysics, Academia Sinica, Graduate School of the Chinese Academy of Sciences, 15 Datun Road, Chaoyang District, Beijing 100101, P.R. China.
Cao
En-Hua
EH
Qin
Jing-Fen
JF
D000080242:8-Hydroxy-2'-Deoxyguanosine; D000111:Acetylcysteine / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D000077237:Arsenic Trioxide; D001152:Arsenicals / Q000494:pharmacology*; D015153:Blotting, Western; D002453:Cell Cycle / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D045744:Cell Line, Tumor; D003849:Deoxyguanosine / Q000031:analogs & derivatives / Q000096:biosynthesis; D005434:Flow Cytometry; D016195:G2 Phase / Q000187:drug effects; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D018625:Microscopy, Atomic Force; D010087:Oxides / Q000494:pharmacology*; D011485:Protein Binding / Q000187:drug effects; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016615:Telomere / Q000235:genetics / Q000378:metabolism; D035321:Telomeric Repeat Binding Protein 1 / Q000235:genetics* / Q000378:metabolism; D035341:Telomeric Repeat Binding Protein 2 / Q000235:genetics* / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism; D015854:Up-Regulation
D000970:Antineoplastic Agents; D001152:Arsenicals; D010087:Oxides; D012333:RNA, Messenger; D017382:Reactive Oxygen Species; D035321:Telomeric Repeat Binding Protein 1; D035341:Telomeric Repeat Binding Protein 2; D016159:Tumor Suppressor Protein p53; D000080242:8-Hydroxy-2'-Deoxyguanosine; D003849:Deoxyguanosine; D000077237:Arsenic Trioxide; D000111:Acetylcysteine