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Sulforaphane inhibits thyroid cancer cell growth and invasiveness through the reactive oxygen species-dependent
Liping Wang1,2, Zhufang Tian2, Qi Yang1
1Department of Endocrinology, The First Affiliated Hospital of Xi'an Jiaotong University School of Medicine, Xi'an 710061, P.R. China.
Abstract:
Sulforaphane (SFN), a natural compound derived from broccoli/broccoli sprouts, has been demonstrated to be used as an antitumor agent in different types of cancers. However, its antitumor effect in thyroid cancer remains largely unknown. The aim of the study was to investigate the therapeutic potential of SFN for thyroid cancer and explore the mechanisms underlying antitumor effects of SFN by in vitro and in vivo studies. Our data demonstrated that SFN significantly inhibited thyroid cancer cell proliferation in a dose- and time-dependent manner, induced G2/M phase cell cycle arrest and apoptosis, and inhibited thyroid cancer cell migration and invasion by suppressing epithelial-mesenchymal transition (EMT) process and expression of Slug, Twist, MMP-2 and -9. Mechanically, SFN inhibited thyroid cancer cell growth and invasiveness through repressing phosphorylation of Akt, enhancing p21 expression by the activation of Erk and p38 signaling cascades, and promoting mitochondrial-mediated apoptosis via reactive oxygen species (ROS)-dependent pathway. Growth of xenograft tumors derived from thyroid cancer cell line FTC133 in nude mice was also significantly inhibited by SFN. Importantly, we did not find significant effect of SFN on body weight and liver function of mice. Collectively, we for the first time demonstrate that SFN is a potentially effective antitumor agent for thyroid cancer.
Insights
Sulforaphane (SFN), a broccoli-derived compound, shows significant potential as an antitumor agent for thyroid cancer. This study demonstrates SFN
Area of Science:
- Oncology
- Molecular Biology
- Biochemistry
Background:
- Thyroid cancer is a prevalent malignancy with limited therapeutic options.
- Sulforaphane (SFN), a natural compound from broccoli, exhibits antitumor properties in various cancers.
- The therapeutic potential of SFN in thyroid cancer is largely unexplored.
Purpose of the Study:
- To investigate the antitumor effects of SFN on thyroid cancer.
- To elucidate the underlying molecular mechanisms of SFN's action in thyroid cancer.
- To evaluate the efficacy of SFN in preclinical models of thyroid cancer.
Main Methods:
- In vitro studies using thyroid cancer cell lines to assess proliferation, cell cycle, apoptosis, migration, and invasion.
- In vivo studies using a xenograft mouse model to evaluate tumor growth inhibition.
- Western blot analysis and signaling pathway assays to explore molecular mechanisms.
Main Results:
- SFN significantly inhibited thyroid cancer cell proliferation, induced G2/M cell cycle arrest, and promoted apoptosis.
- SFN suppressed thyroid cancer cell migration and invasion by inhibiting epithelial-mesenchymal transition (EMT) and downregulating Slug, Twist, MMP-2, and MMP-9.
- SFN repressed Akt phosphorylation, enhanced p21 expression via Erk and p38 activation, and promoted ROS-dependent mitochondrial apoptosis.
- SFN significantly inhibited xenograft tumor growth in mice without adverse effects on body weight or liver function.
Conclusions:
- SFN demonstrates significant antitumor activity against thyroid cancer in vitro and in vivo.
- SFN exerts its effects by modulating key signaling pathways involved in cell cycle, apoptosis, and EMT.
- SFN represents a promising natural compound for the development of novel thyroid cancer therapies.
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