Arctigenin Enhances Chemosensitivity to Cisplatin in Human Nonsmall Lung Cancer H460 Cells through Downregulation of Survivin Expression

Abstract

Arctigenin, a dibenzylbutyrolactone lignan, enhances cisplatin-mediated cell apoptosis in cancer cells. Here, we sought to investigate the effects of arctigenin on cisplatin-treated non-small-cell lung cancer (NSCLC) H460 cells. The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay and annexin-V/propidium iodide staining were performed to analyze the proliferation and apoptosis of H460 cells. Arctigenin dose-dependently suppressed cell proliferation and potentiated cell apoptosis, coupled with increased cleavage of caspase-3 and poly(ADP-ribose) polymerase. Moreover, arctigenin sensitized H460 cells to cisplatin-induced proliferation inhibition and apoptosis. Arctigenin alone or in combination with cisplatin had a significantly lower amount of survivin. Ectopic expression of survivin decreased cell apoptosis induced by arctigenin (P < 0.05) or in combination with cisplatin (P < 0.01). Moreover, arctigenin (P < 0.05) or in combination with cisplatin (P < 0.01) induced G1/G0 cell-cycle arrest. Our data provide evidence that arctigenin has a therapeutic potential in combina-tion with chemotherapeutic agents for NSLC.

Arctigenin inhibits prostate tumor cell growth in vitro and in vivo

“…Both were detected in rat plasma after oral administration of arctiin and distributed widely in different tissues including small intestine, stomach, lung and kidney 11 . The anti-carcinogenic activity of Arc has been demonstrated in vitro and in a few animal studies in several cancers, including pancreatic, breast, and lung cancer, associated with the induction of apoptosis, inhibition of proliferation and modulations of multiple signaling pathways 12-14 . We previously demonstrated in vitro in prostate cancer that the combination with Arc at lower doses significantly enhanced the anti-proliferative effect of several other phytochemicals like curcumin, green tea polyphenols, and quercetin 15,16 .…”

Recent Advances on Small-Molecule Survivin Inhibitors

“…Arctigenin, a ligand isolated from the seeds of Arctium lappa , shows anti-proliferative activities against a series of cancers [60, 61]. A study illustrates the mechanism of its anticancer effect [61].…”

“…The level of survivin was significantly reduced in arctigenin-treated ovarian cancer cells. Arctigenin has also been shown to sensitize tumor cells to cisplatin treatment by inhibiting survivin [60]. …”

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

“…The level of survivin was significantly reduced in arctigenin-treated ovarian cancer cells. Arctigenin has also been shown to sensitize tumor cells to cisplatin treatment by inhibiting survivin [187].…”

“…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].…”