Inactivation of Akt by arsenic trioxide induces cell death via mitochondrial-mediated apoptotic signaling in SGC-7901 human gastric cancer cells.
Arsenic trioxide (As2O3) has been recognized as a potential chemotherapeutic agent, yet the details concerning its mechanism of action in solid cancers remain undetermined. The present study assessed the role of Akt in the cell death induced by As2O3. The MTT assay showed that As2O3 suppressed the proliferation of SGC-7901 cells in a dose- and time-dependent manner. Characteristic apoptotic changes were observed in the As2O3‑treated cells by Hoechst 33342 staining, and FACS analysis showed that As2O3 caused dose-dependent apoptotic cell death. As2O3 activated caspase-3 and -9, and PARP cleavage in a dose-dependent manner. Compromised mitochondrial membrane potential and an increased protein level of Bax indicated involvement of mitochondia. As2O3 decreased the levels of p-Akt (Ser473), p-Akt (Thr308) and p-GSK-3β (Ser9), suggesting that As2O3 inactivated Akt kinase. In addition, LY294002 (a PI3 kinase inhibitor) augmented the apoptosis induced by As2O3. These results demonstrated that inhibition of PI3K/Akt signaling was involved in As2O3-induced apoptosis of gastric cancer SGC-7901 cells.
The Center for Endemic Disease Control, Chinese Center for Disease Control and Prevention, Harbin Medical University, Harbin, Heilongjiang 150081, P.R. China.
Yan-Hui
YH
Gao
Department of Surgery, The Second Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang 150081, P.R. China.
Hao-Peng
HP
Zhang
Department of Outpatient Surgery, Linyi People's Hospital, Linyi, Shandong 276003, P.R. China.
Shu-Meng
SM
Yang
Cancer Research Institute, Harbin Medical University, Harbin, Heilongjiang 150081, P.R. China.
Yue
Y
Yang
Cancer Research Institute, Harbin Medical University, Harbin, Heilongjiang 150081, P.R. China.
Yu-Yan
YY
Ma
Department of Surgery, The Second Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang 150081, P.R. China.
Xin-Yu
XY
Zhang
Cancer Research Institute, Harbin Medical University, Harbin, Heilongjiang 150081, P.R. China.
Yan-Mei
YM
Yang
D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D000077237:Arsenic Trioxide; D001152:Arsenicals / Q000494:pharmacology*; D015153:Blotting, Western; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D006801:Humans; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D008928:Mitochondria / Q000187:drug effects* / Q000378:metabolism; D010087:Oxides / Q000494:pharmacology*; D051057:Proto-Oncogene Proteins c-akt; D015398:Signal Transduction / Q000187:drug effects*; D013274:Stomach Neoplasms / Q000378:metabolism*
D000970:Antineoplastic Agents; D001152:Arsenicals; D010087:Oxides; D051057:Proto-Oncogene Proteins c-akt; D000077237:Arsenic Trioxide