Triptolide exerts an anti-tumor effect on non‑small cell lung cancer cells by inhibiting activation of the IL‑6/STAT3 axis

Abstract

Lung cancer is the leading cause of cancer-associated mortality and current treatments are not sufficiently effective. Numerous studies have revealed that triptolide (TP), a classical traditional chinese medicine compound widely used as an anti-inflammatory and antirheumatic drug, also has an antitumor effect. This effect is hypothesized to be mediated by multiple pathways, with signal transducer and activator of transcription 3 (STAT3) possibly one of them. Evidence indicates that STAT3 participates in the initiation and progression of lung cancer during cell proliferation, apoptosis and migration; however, whether and how TP affects STAT3 and its targets remain unclear. In this study, the potential role of TP in the proliferation, apoptosis, and migration of non-small cell lung cancer cell lines was investigated and evaluated the impact of TP on the interleukin-6 (IL-6)/STAT3 axis. The results showed that TP inhibited cell proliferation and migration and induced apoptosis. TP decreased the phosphorylation of STAT3, inhibited STAT3 translocation into the nucleus, and reduced the expression of STAT3 target genes involved in cell survival, apoptosis and migration, e.g. C-myc, BCL-2, myeloid cell leukemia-1 (MCL-1), and matrix metallopeptidase 9 (MMP-9). Additionally, IL-6-induced activation of STAT3 target genes (e.g. MCL-1 and BCL-2) was attenuated by TP and homoharringtonine. In conclusion, the effect of TP on STAT3 signaling points to a promising strategy for drug development.

Triptolide impairs LUAD cells through the JAK-STAT signaling pathway by activating autophagy

“…As the main bioactive component of the Chinese herb Tripterygium wilfordii, TPL has shown strong antitumor activities [24], sensitizing effects and inhibited resistance to cancer therapies [25]. Many studies have con rmed that TPL exerts antitumor effects on lung cancer[8- 10,26,27]. In the present study, we rst examined the effect of TPL on autophagy induction in human LUAD cell lines (A549 and NCI-H1299), and we found that TPL treatment signi cantly induced autophagy and subsequently inhibited proliferation, migration and invasion in LUAD cells, while this inhibitory effect was blocked by pretreatment with autophagy inhibitors.…”

Perspectives and controversies regarding the use of natural products for the treatment of lung cancer

“…Tanshinone IIA increases TRAIL‐induced NSCLC cell death by selectively activating PERK/ATF4 and inhibiting the STAT3‐mediated upregulation of DR5 and downregulation of Survivin 247 . TPL also inhibited the phosphorylation of STAT3, inhibited the transport of STAT3 into the nucleus, and reduced the expression of STAT3 target genes associated with apoptosis, migration, and cell survival, such as C‐myc, myeloid leukemia 1 (MCL‐1), BCL2, and matrix metallopeptidase‐9 (MMP‐9), thereby inhibiting cell proliferation and migration and inducing cell apoptosis 248 …”

Triptolide Shows High Sensitivity and Low Toxicity Against Acute Myeloid Leukemia Cell Lines Through Inhibiting WSTF-RNAPII Complex

“…However, the narrow therapeutic window caused by severe systemic toxicity limits its clinical application (3)(4)(5)(6). Some preclinical studies have reported that the IC 50 values of triptolide against cancer cell lines vary (7)(8)(9)(10)(11)(12). The discovery of sensitive cell lines to triptolide may provide a possibility to broaden its safety window and its clinical application.…”