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Updated: May 17, 2025
Spontaneous Murine Model of Anaplastic Thyroid Cancer
Published on: February 3, 2023
Effect of Benzyl Isothiocyanate on Anaplastic Thyroid Cancer Evaluated by Network Pharmacology Combined with
Chunmei Ma1,2, Qicheng Zhang3, Yan Wang4
1Department of Nuclear Medicine, Tianjin Key Lab of Functional Imaging & Tianjin Institute of Radiology, Tianjin Medical University General Hospital, Tianjin 300052, China.
Abstract:
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.
Insights
Benzyl isothiocyanate (BITC), found in cruciferous vegetables, inhibits anaplastic thyroid carcinoma (ATC) growth by promoting apoptosis and disrupting autophagy. This natural compound shows promise for ATC treatment.
Area of Science:
- Oncology
- Molecular Biology
- Pharmacology
Background:
- Benzyl isothiocyanate (BITC) is a natural compound found in cruciferous vegetables with known chemopreventive properties.
- The precise mechanisms by which BITC inhibits tumor cell growth, particularly in anaplastic thyroid carcinoma (ATC), remain incompletely understood.
Purpose of the Study:
- To elucidate the molecular targets and mechanisms of Benzyl isothiocyanate (BITC) in the treatment of anaplastic thyroid carcinoma (ATC).
- To validate the therapeutic potential of BITC against ATC using in vitro and in vivo models.
Main Methods:
- Integrated network pharmacology and molecular docking to identify key targets of BITC in ATC.
- Conducted cellular experiments on ATC cell lines (8505C, CAL-62) to assess BITC's effects on cell viability, apoptosis, and autophagy.
- Utilized a mouse tumor model (CAL-62 xenografts) to evaluate the in vivo efficacy of BITC.
Main Results:
- Identified 10 key targets for BITC in ATC, primarily associated with the nuclear factor-κB (NF-κB) and apoptosis signaling pathways.
- BITC demonstrated dose- and time-dependent inhibition of ATC cell growth, with IC50 values around 28 μmol/L.
- BITC induced apoptosis in ATC cells and significantly enhanced growth inhibition when combined with the autophagy inhibitor 3MA, while HCQ showed no significant enhancement.
- BITC administration in a mouse model significantly suppressed tumor growth.
Conclusions:
- Benzyl isothiocyanate (BITC) effectively inhibits anaplastic thyroid carcinoma (ATC) cell growth both in vitro and in vivo.
- BITC exerts its anti-tumor effects by disrupting autophagic degradation, inhibiting the NF-κB pathway, and promoting apoptosis in ATC cells.
- These findings highlight BITC as a potential therapeutic agent for anaplastic thyroid carcinoma.
