Abstract
Esophageal cancer is one of the most common cancer with limited therapeutic strategies, thus it is important to develop more effective strategies to against it. Sulforaphene (SFE), an isothiocyanate isolated from radish seeds, was proved to inhibit esophageal cancer progression in the current study. Flow cytometric analysis showed SFE induced cell apoptosis and cycle arrest in G2/M phase. Also, scrape motility and transwell assays presented SFE reduced esophageal cancer cell metastasis. Microarray results showed the influence of SFE on esophageal cancer cells was related with stearoyl-CoA desaturase (SCD), cadherin 3 (CDH3), mitogen-activated protein kinase kinase 3 (MAP2K3) and growth arrest and DNA damage inducible beta (GADD45B). SCD and CDH3 could promote esophageal cancer metastasis via activating the Wnt pathway, while the latter one was involved in a positive feedback loop, GADD45B-MAP2K3-p38-p53, to suppress esophageal cancer growth. GADD45B was known to be the target gene of p53, and we proved in this study, it could increase the phosphorylation level of MAP2K3 in esophageal cancer cells, activating p38 and p53 in turn. SFE treatment elevated MAP2K3 and GADD45B expression and further stimulated this feedback loop to better exert antitumor effect. In summary, these results demonstrated that SFE had the potential for developing as a chemotherapeutic agent because of its inhibitory effects on esophageal cancer metastasis and proliferation.
Highlights
Introduction Esophageal cancer is the top10 global arising common cancer and multiple studies suggest that excessive smoking, hot tea and red meat consumption, poor oral health, and low intake of fresh fruits and vegetables are associated with a high risk of it
We examined the role of SFE in four esophageal cancer cell lines, finding a dosedependent inhibition of SFE on cell proliferation (Supplementary Fig. S1A)
As the mitochondrial pathway and the death receptor pathway are reported to mediate caspases activation, and caspase-9 and caspase-8 belonged to the two pathways respectively[21,22], we predicted SFE induced mitochondrial apoptosis in esophageal cancer cells and measured the mitochondrial membrane potential, the decrease of which was a characteristic performance in mitochondrial apoptosis
Summary
Introduction Esophageal cancer is the top10 global arising common cancer and multiple studies suggest that excessive smoking, hot tea and red meat consumption, poor oral health, and low intake of fresh fruits and vegetables are associated with a high risk of it. Sulforaphene (SFE), as an isothiocyanate isolated from radish seeds[4,5], was proved to possess strong anticarcinogenic activities. It could induce apoptosis in lung cancer cell lines by inhibiting the PI3K-Akt pathway[6] and cause hepatocellular carcinoma cell death through repressing keratin 8 and activating anoikis[7]. It is Official journal of the Cell Death Differentiation Association
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