Rapamycin suppresses ROS-dependent apoptosis caused by selenomethionine in A549 lung carcinoma cells

Maiko Suzuki, Manabu Endo, Fumiaki Shinohara, Seishi Echigo, Hidemi Rikiishi

研究成果: Article査読

23 被引用数 (Scopus)

抄録

Purpose: Although selenium compounds possess chemotherapeutic features by inducing apoptosis in cancer cells with trivial side effects on normal cells, the mechanisms underlying its anti-cancer activity are insufficiently understood at the present. In this study, we investigated the effects of rapamycin on apoptosis induced by seleno-L-methionine (SeMet) or selenite in A549 cells. Methods: The effects of Se compounds, SeMet and selenite, on cell proliferation, apoptosis and its signaling pathway were investigated in established human adenocarcinoma cell line (A549). Cancer cells were treated with each Se during different periods. Cell apoptosis and signaling molecules were analyzed by flow cytometry (TUNEL method) or immunoblotting, respectively. Results: SeMet induces reactive oxygen species generation associated with the induction of apoptosis, because pretreatment of cells with N-acetyl-L-cysteine completely blocked SeMet-induced apoptosis. We also found that rapamycin completely suppressed the apoptosis of cells treated by SeMet, but not selenite. SeMet-induced apoptosis is significantly downregulated in combination with PI3 K family inhibitors (LY294002, wortmannin, PI-103, and 3-methyladenine). In addition, ROS generation was included in downstream signaling events associated with the phosphorylation of mTOR, because pretreatment of cells with rapamycin inhibited ROS generation. Conclusion: These results suggest that SeMet-induced apoptosis is affected by the Akt/mTOR/ROS pathway in A549 cells. Akt serves an anti-survival function in the system of SeMet-treated lung cancer cells, but autophagic signaling remained unsolved.

本文言語English
ページ(範囲)1129-1136
ページ数8
ジャーナルCancer Chemotherapy and Pharmacology
67
5
DOI
出版ステータスPublished - 2011 5

ASJC Scopus subject areas

  • Oncology
  • Toxicology
  • Pharmacology
  • Cancer Research
  • Pharmacology (medical)

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