Arctigenin Promotes Apoptosis in Ovarian Cancer Cells via the iNOS/NO/STAT3/Survivin Signalling

Abstract

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.

Arctigenin, a natural lignan compound, induces G0/G1 cell cycle arrest and apoptosis in human glioma cells

“…Concordantly, arctigenin-mediated apoptosis was significantly inhibited by pretreatment of the U87MG and T98G cells with Z-DEVD-FMK, a caspase-3 inhibitor, indicating that the arctigenin-induced apoptosis of glioma cells may be mediated via caspase-3 activation. The pro-apoptotic activity of arctigenin has also been demonstrated in numerous other types of cancer, including breast and ovarian cancer (8,10,20).…”

“…Arctigenin has demonstrated anticancer activities in numerous types of cancer, including gastric cancer (8), breast cancer (9) and ovarian cancer (10). However, the effects of arctigenin on the aggressive phenotypes of human glioma cells remain unclear.…”

Epigenetic mechanism of survivin dysregulation in human cancer

“…The 10 most studied transcription factors and their relevant binding sites are shown in figure 1. The functional binding sites for Sp1 (Chen et al, 2011; Cheng et al, 2012; Zhang et al, 2015), NF-κB (Angileri et al, 2008; Papanikolaou et al, 2011; Wang et al, 2010), Stat3 (Huang et al, 2014; Kim et al, 2016), Rb (Raj et al, 2008; Yang et al, 2008), p53 (Vaziri et al, 2005; Zhou et al, 2002), and Egr1 (Wagner et al, 2008b) have been found in BIRC5 gene promoter, suggesting a possible involvement of these factors in direct control of BIRC5 gene expression. Among them, Sp1, Stat3 and NF-κB activate expression of BIRC5 gene.…”

Discovery of Novel Tubulin Polymerization Inhibitors and Survivin Inhibitors as Potential Anticancer Agents

“…Arctigenin, a ligand isolated from the seeds of Arctium lappa, shows antiproliferative activities against a series of cancers [187][188]. A study illustrates the mechanism of its anticancer effect [188].…”

“…A study illustrates the mechanism of its anticancer effect [188]. The results showed that arctigenin executed its antitumor effect by inhibiting STAT3 phosphorylation and survivin expression.…”