In vitro and In vivo evaluation of signaling pathways underlying the tumor suppressive effect of benzyl isothiocyanate in anaplastic thyroid carcinoma

Anaplastic thyroid carcinoma (ATC) is a rare and aggressive form of thyroid cancer. It is often considered one of the most aggressive cancers known, with a very poor prognosis. ATC is characterized by its rapid growth and invasion into surrounding tissues. It is often diagnosed at an advanced stage when it has already spread to nearby structures in the neck, making it challenging to treat. Due to its rarity and aggressive nature, anaplastic thyroid cancer is a difficult condition to treat and requires an early diagnostic approach and timely intervention, therefore knowledge of the mechanisms underlying thyroid cancer progression and identification of new therapeutic targets represent important research challenges. Benzyl isothiocyanate (BITC) is a naturally occurring compound found in cruciferous vegetables that has shown promise for its potential anticancer properties. The aim of this study was to evaluate the antitumor effect of BITC in thyroid cancer, highlighting signaling pathways involved in BITC mechanism of action, and identify new therapeutic strategies for the treatment of the most common endocrine cancer. The study examined how BITC interacts with specific signaling pathways, including mTOR (mammalian target of rapamycin) and MAPK (mitogen-activated protein kinase). These pathways are often dysregulated in cancer and can be targeted for therapeutic purposes. This work included in vitro and in vivo studies. The in vitro model was performed using different TC cell lines to study the effect of BITC on the modulation of autophagy, through direct interaction with mTOR and MAPK pathways, and to evaluate its ability to modulate apoptosis and reduce cell migration. To confirm the in vitro findings and better mimic the complex tumor microenvironment, an in vivo orthotopic model of ATC was used. This involved the in-situ inoculation of ATC cells in mice, followed by treatment with BITC. Histological analysis of the mouse thyroids was conducted to evaluate the effects of BITC on tumor growth and progression and Western blot analysis was used to examine markers related to autophagy, apoptosis, and epithelial-mesenchymal transition (EMT). The study's results indicate that BITC, both in vitro and in vivo, has the potential to slow the progression of anaplastic thyroid cancer. This effect appears to be mediated through interactions with autophagy pathways, reduction in EMT, and the attenuation of tumor-related inflammation. In conclusion, this study provides valuable insights into the potential role of BITC as a therapeutic agent for anaplastic thyroid carcinoma. It highlights the importance of understanding the molecular mechanisms underlying cancer progression and identifies BITC as a compound worth further investigation for the development of new treatment strategies for this aggressive form of thyroid cancer.