Effect of Benzyl Isothiocyanate on Anaplastic Thyroid Cancer Evaluated by Network Pharmacology Combined with Experiments

Benzyl isothiocyanate (BITC), a natural compound abundant in cruciferous vegetables, plays an important role in the chemoprevention of various human malignancies. However, the mechanism by which BITC inhibits tumor cell growth is not fully understood. This study combined network pharmacology, molecular docking, cellular experiments, and mouse tumor models to predict and validate the targets and mechanisms of BITC in the treatment of anaplastic thyroid carcinoma (ATC). A total of 10 key targets of BITC and ATC were selected for molecular docking. The key target genes of KEGG were mainly concentrated in the nuclear factor κB signaling pathway and apoptosis signaling pathway. The inhibitory effects of BITC on two ATC cell lines, 8505C and CAL-62, were dose-dependent and time-dependent, with IC50 values of 27.56 and 28.30 μmol/L, respectively. BITC induced apoptosis in ATC cells. Pretreatment with autophagy inhibitor 3MA (2 mmol/L) significantly enhanced growth inhibition caused by BITC in ATC cells. Another autophagy inhibitor, HCQ (20 μmol/L), did not enhance the inhibitory effect of BITC. In CAL-62 xenografted nude mice, BITC (100 mg·kg-1·d-2, ip) significantly inhibited tumor growth. Our results indicate that BITC can inhibit the growth of ATC cells both in vitro and in vivo. Additionally, BITC disrupts autophagic degradation in ATC cells, inhibits the NF-κB pathway, and promotes apoptosis.