Abstract
Non-small-cell lung cancer (NSCLC) is a prevalent malignant tumor with high morbidity and mortality rates worldwide. Although surgical resection, adjuvant radiotherapy/chemotherapy, and targeted molecular therapy are the cornerstones of NSCLC treatment, NSCLC is associated with high recurrence rates and drug resistance. This study analyzed the potential targets and pathways of 6-Shogaol (6-SH) in NSCLC, showing that 6-SH binds to heat-shock 60 kDa protein (HSP60) in A549 cells, induces cell apoptosis, and arrests the cell cycle possibly by disrupting the mitochondrial function. HSP60 was identified as the target of 6-SH and 6-SH-induced HSP60 degradation which was mediated by the proteasome. The binding of 6-SH with HSP60 altered its stability, inhibited the ERK, Stat3, PI3K, Akt, and mTOR signaling pathways, and Tax acted synergistically with 6-SH, indicating that 6-SH could be developed as a potential therapeutic agent for an NSCLC treatment.