Author:
Wu Xiang,Zhu Yu,Yan Huiqin,Liu Boning,Li Ying,Zhou Qinghua,Xu Ke
Abstract
Abstract
Background
Isothiocyanates are natural compounds found in consumable cruciferous vegetables. They have been shown to inhibit chemical carcinogenesis by a wide variety of chemical carcinogens in animal models. Recent studies have also shown that isothiocyanates have antitumor activity, inhibiting the growth of several types of cultured human cancer cells. Our previous study showed that PEITC inhibited human leukemia cells growth by inducing apoptosis. However, the effect of isothiocyanates on lung cancer cell metastasis has not been studied. In the present study, we investigated the inhibitory effects of BITC and PEITC on metastatic potential of highly metastatic human lung cancer L9981 cells.
Methods
Cell migration and invasion were measured by wound healing assay and transwell chemotaxis assay. Expression of metastasis-related genes was assessed by quantitative RT-PCR and Western blotting. The mechanisms of action were evaluated by flow cytometry, reporter assay and Western blotting.
Results
Our data showed that both BITC and PEITC inhibited L9981 cell growth in a dose-dependent manner, the IC50 values were 5.0 and 9.7 μM, respectively. Cell migrations were reduced to 8.1% and 16.5% of control, respectively; and cell invasions were reduced to 2.7% and 7.3% of control, respectively. Metastasis-related genes MMP-2, Twist and β-catenin were also modulated. BITC and PEITC inhibited cell survival signaling molecules Akt and NFκB activation. Moreover, BITC and PEITC increased ROS generation and caused GSH depletion. Pretreatment with NAC blocked BITC and PEITC induced ROS elevation and NFκB inhibition.
Conclusion
Our results indicated that BITC and PEITC suppress lung cancer cell metastasis potential by modulation of metastasis-related gene expression, inhibition of Akt/NFκB pathway. Induction of oxidative stress may play an important role.
Publisher
Springer Science and Business Media LLC
Subject
Cancer Research,Genetics,Oncology
Reference55 articles.
1. Stewart BWKP: WHO. World Cancer Report. 2003, IARC Press, Lyon, France
2. Parkin DMBF, Ferlay J, Pisani P: Global cancer statistics, 2002. CA Cancer J Clin. 2005, 55 (2): 74-108. 10.3322/canjclin.55.2.74.
3. Ries LEM, Kosary C, et al: Cancer Statistics Review, 1975-2002. 2005, National Cancer Institute
4. Jemal Aea: Cancer statistics, 2005. CA. Cancer J Clin. 2005, 55: 10-30. 10.3322/canjclin.55.1.10.
5. Gupta GP, Massague J: Cancer metastasis: building a framework. Cell. 2006, 127 (4): 679-695. 10.1016/j.cell.2006.11.001.
Cited by
89 articles.
订阅此论文施引文献
订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献