Using an integrated multi-omics approach (transcriptomics, proteomics, lysine acetyl-proteomics) in resistant GBM cells and validating findings in vitro and in AB strain zebrafish (<i>Danio rerio</i>) xenografts, we found that Alisol B induces endoplasmic reticulum stress and G2/M arrest, initiated by extensive lysine acetylation reprogramming on histones and metabolic enzymes (e.g., FASN, FDFT1). Here, FASN is linked to glioblastoma.