Mechanism investigation of Caspase-8/GSDMC dependent immunogenic cell death induced by Ophiopogonin B in NSCLC cells

• Main Authors: Zhihui Li (Author), Ling Gu (Author), Qian Gao (Author), Liqiu Li (Author), Maozheng Sheng (Author), Yuyan Ling (Author), Cheng Hu (Author), Menglin He (Author), Xiongfei Zhang (Author), Xu Shen (Author), Xu Zhang (Author), Meijuan Chen (Author)
• Format: Book
• Published: Elsevier, 2022-09-01T00:00:00Z.
• Subjects: article
• Online Access: Connect to this object online.

Summary

Ophiopogonin B (OP-B) as a bioactive component of Radix Ophiopogon Japonicus has been reported to induce various kinds of cell death of non-small cell lung cancer (NSCLC) cells, while the underline mechanism is unknown. Herein, through affinity chromatography, Biolayer Interferometry (BLI), and molecular docking simulation technology, we verified HSP90-α to be the potential target of OP-B in A549 cells. Further investigation indicated that HSP90-α promoted translocation of STAT3 to the nuclear and further promoted the expression of GSDMC, which enhanced its competitive binding to Caspase-8, and at last resulted in pyroptosis of the cell. In addition, investigation in A549 orthotopic tumor nude and NCG mice model verified that OP-B-induced pyroptosis of cancer cells leaded to recruitment of NK cells to lung cancer tissue. Taken together, through targeting at HSP90-α, OP-B induced Caspase-8/GSDMC dependent pyroptosis and further resulted in ICD of A549 cells in vitro and in vivo.

Item Description

2667-1425
10.1016/j.prmcm.2022.100157