Anti-tumor Activity of Schoenoplectus triqueter Extract by Suppressing the STAT3 Signaling Pathway in A549 Lung Adenocarcinoma Cells

Many plant extracts have been recognized for their potential anti-cancer properties. Schoenoplectus triqueter (L.) Palla, commonly known as triangular rush (TAR) and part of the Cyperaceae family, predominantly thrives in the wetlands of the Huangpu Yangtze estuary. In this study, we explored the anti-cancer capabilities of TAR on lung cancer A549 cells. Our findings revealed that TAR was significantly more cytotoxic to A549 cells than to normal lung HEL 299 cells. TAR promoted apoptosis through enhanced caspase-3 activity and subsequent cleavage of poly ADP ribose polymerase (PARP). This apoptotic effect was associated with the downregulation of several STAT3-regulated genes, including Survivin, IAP-1, Cyclin D1, COX-2, and matrix metallopeptidase 9 (MMP-9). Moreover, TAR effectively reduced cell proliferation, invasion, and migration. The inhibition of STAT3 activation was achieved by blocking the upstream Janus activated kinases 1 and 2 (JAK1, JAK2), c-Src kinases, and the nuclear translocation of STAT3 in A549 cells. Additionally, TAR enhanced the effects of cisplatin through synergistic inhibition of STAT3 activation and increased apoptosis in A549 cells. Key compounds contributing to these biological activities were identified via LC-HRMS analysis. Our results suggest that TAR blocks constitutive STAT3 activation, exhibiting anti-proliferative and pro-apoptotic effects in lung cancer A549 cells.