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

Abstract

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.

Keywords

• Non-small cell lung cancer (NSCLC)
• Immunogenic cell death (ICD)
• Pyroptosis
• Ophiopogonin B (OP-B)
• HSP90-α