Arctigenin promotes apoptosis in ovarian cancer cells via the iNOS/NO/STAT3/survivin signalling.
Arctigenin is a biologically active lignan extracted from the seeds of Arctium lappa and shows anticancer activity against a variety of human cancers. The aim of this study was to determine the effects of arctigenin on ovarian cancer cell proliferation and survival and associated molecular mechanisms. Human ovarian cancer OVCAR3 and SKOV3 cells were treated with arctigenin, and cell proliferation and apoptosis were assessed. Western blot analysis was used to examine signal transducer and activator of transcription-3 (STAT3) phosphorylation and survivin and inducible nitric oxide synthase (iNOS) expression. The involvement of STAT3/survivin/iNOS/NO signalling in arctigenin action was checked. Arctigenin treatment resulted in a significant and dose-dependent inhibition of cell proliferation. Arctigenin-treated cells showed a 4-6 times increase in the percentage of apoptosis, compared with control cells. Pre-treatment with Ac-DEVD-CHO, a specific inhibitor of caspase-3, counteracted the induction of apoptosis by arctigenin. Arctigenin treatment significantly inhibited STAT3 phosphorylation and survivin and iNOS expression. Arctigenin-induced apoptosis was impaired by pre-transfection with survivin-expressing plasmid or addition of chemical nitric oxide (NO) donors. Additionally, exogenous NO prevented the suppression of STAT3 phosphorylation and survivin expression by arctigenin. Arctigenin treatment inhibits the proliferation and induces caspase-3-dependent apoptosis of ovarian cancer cells. Suppression of iNOS/NO/STAT3/survivin signalling is causally linked to the anticancer activity of arctigenin. Therefore, arctigenin may be applicable to anticancer therapy for ovarian cancer.
Department of Obstetrics and Gynecology, Chinese PLA General Hospital, Beijing, China.
Ke
K
Huang
Li-an
LA
Li
Yuan-guang
YG
Meng
Yan-qin
YQ
You
Xiao-yu
XY
Fu
Lei
L
Song
D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology* / Q000627:therapeutic use; D017209:Apoptosis / Q000187:drug effects*; D015153:Blotting, Western; D053148:Caspase 3 / Q000378:metabolism; D045744:Cell Line, Tumor; D005260:Female; D005663:Furans / Q000494:pharmacology* / Q000627:therapeutic use; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins / Q000187:drug effects*; D017705:Lignans / Q000494:pharmacology* / Q000627:therapeutic use; D009569:Nitric Oxide / Q000037:antagonists & inhibitors*; D052247:Nitric Oxide Synthase Type II / Q000187:drug effects*; D010051:Ovarian Neoplasms / Q000188:drug therapy*; D050796:STAT3 Transcription Factor / Q000187:drug effects*; D015398:Signal Transduction / Q000187:drug effects*; D000077022:Survivin
D000972:Antineoplastic Agents, Phytogenic; C107489:BIRC5 protein, human; D005663:Furans; D051034:Inhibitor of Apoptosis Proteins; D017705:Lignans; D050796:STAT3 Transcription Factor; D000077022:Survivin; D009569:Nitric Oxide; D052247:Nitric Oxide Synthase Type II; D053148:Caspase 3; C071942:arctigenin