Antiproliferative effect of gold(I) compound auranofin through inhibition of STAT3 and telomerase activity in MDA-MB 231 human breast cancer cells.
Signal transducer and activator of transcription 3 (STAT3) and telomerase are considered attractive targets for anticancer therapy. The in vitro anticancer activity of the gold(I) compound auranofin was investigated using MDA-MB 231 human breast cancer cells, in which STAT3 is constitutively active. In cell culture, auranofin inhibited growth in a dose-dependent manner, and N-acetyl-L-cysteine (NAC), a scavenger of reactive oxygen species (ROS), markedly blocked the effect of auranofin. Incorporation of 5-bromo-2'-deoxyuridine into DNA and anchorage-independent cell growth on soft agar were decreased by auranofin treatment. STAT3 phosphorylation and telomerase activity were also attenuated in cells exposed to auranofin, but NAC pretreatment restored STAT3 phosphorylation and telomerase activity in these cells. These findings indicate that auranofin exerts in vitro antitumor effects in MDA-MB 231 cells and its activity involves inhibition of STAT3 and telomerase. Thus, auranofin shows potential as a novel anticancer drug that targets STAT3 and telomerase.
Department of Medical Lifescience, College of Medicine, The Catholic University of Korea, Seoul, Korea.
Nam-Hoon
NH
Kim
Hyo Jung
HJ
Park
Mi-Kyung
MK
Oh
In-Sook
IS
Kim
D000111:Acetylcysteine / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000633:toxicity*; D001310:Auranofin / Q000633:toxicity*; D001943:Breast Neoplasms / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D015536:Down-Regulation; D005260:Female; D006046:Gold / Q000737:chemistry; D006801:Humans; D010766:Phosphorylation / Q000187:drug effects; D050796:STAT3 Transcription Factor / Q000037:antagonists & inhibitors* / Q000378:metabolism; D019098:Telomerase / Q000037:antagonists & inhibitors* / Q000378:metabolism
D000970:Antineoplastic Agents; D050796:STAT3 Transcription Factor; D001310:Auranofin; D006046:Gold; D019098:Telomerase; D000111:Acetylcysteine