The sesquiterpene lactone eupatolide induces apoptosis in non-small cell lung cancer cells by suppressing STAT3 signaling

Abstract

We aimed to evaluate the role of a natural sesquiterpene lactone, eupatolide, in non-small-cell lung cancer (NSCLC) and further explore its underlying mechanism on regulating the activation of signal transducer and activator of transcription 3 (STAT3), which is thought to have carcinogenic function in a variety of malignancies including lung cancer. Cell survival was measured by Cell Counting Kit-8 assay. in vivo experiments were performed by inoculating NSCLC cells into nude mice. Western blot and qRT-PCR were applied to detect the activation level of STAT3 and the mRNA levels of anti-apoptotic markers. The cell apoptosis was measured by Annexin V-FITC/PI Apoptosis Detection Kit. Our results showed that eupatolide suppressed the survival of NSCLC cells in a dose and time dependent manner. Furthermore, eupatolide increased the anti-tumor activity of the chemotherapeutic drugs cisplatin and 5-Fluoracil (5-FU). The xenograft study revealed that eupatolide suppressed tumor growth of NSCLC cells in vivo. Furthermore, eupatolide induced apoptosis by suppressing the activation of STAT3 in NSCLC cells. Sustained activation or knockdown of STAT3 suppressed and enhanced the activity of eupatolide, respectively. This paper is the first to report that eupatolide could effectively inhibit NSCLC progression, suggesting that eupatolide might be utilized as a novel STAT3 inhibitor for treating NSCLC.

Keywords: Cell apoptosis; Eupatolide; Non-small-cell lung cancer (NSCLC); Sesquiterpene lactone; Signal transducer and activator of transcription 3 (STAT3).