Sulforaphane inhibits thyroid cancer cell growth and invasiveness through the reactive oxygen species-dependent pathway

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 potent...

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Veröffentlicht in:Oncotarget 2015-09, Vol.6 (28), p.25917-25931
Hauptverfasser: Wang, Liping, Tian, Zhufang, Yang, Qi, Li, Heng, Guan, Haixia, Shi, Bingyin, Hou, Peng, Ji, Meiju
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container_end_page 25931
container_issue 28
container_start_page 25917
container_title Oncotarget
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creator Wang, Liping
Tian, Zhufang
Yang, Qi
Li, Heng
Guan, Haixia
Shi, Bingyin
Hou, Peng
Ji, Meiju
description 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.
doi_str_mv 10.18632/oncotarget.4542
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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. 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subjects Animals
Anticarcinogenic Agents - pharmacology
Apoptosis - drug effects
Apoptosis Regulatory Proteins - genetics
Blotting, Western
Cell Cycle Checkpoints - drug effects
Cell Line, Tumor
Cell Proliferation - drug effects
Dose-Response Relationship, Drug
Female
Gene Expression Regulation, Neoplastic - drug effects
Humans
Isothiocyanates - pharmacology
Membrane Potential, Mitochondrial - drug effects
Mice, Nude
Mitogen-Activated Protein Kinases - metabolism
Neoplasm Invasiveness
Reactive Oxygen Species - metabolism
Research Paper
Reverse Transcriptase Polymerase Chain Reaction
Signal Transduction - drug effects
Thyroid Neoplasms - drug therapy
Thyroid Neoplasms - genetics
Thyroid Neoplasms - metabolism
Time Factors
Tumor Burden - drug effects
Tumor Cells, Cultured
Xenograft Model Antitumor Assays
title Sulforaphane inhibits thyroid cancer cell growth and invasiveness through the reactive oxygen species-dependent pathway
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