title: Benzyl isothiocyanate inhibits breast cancer cell tumorigenesis via repression of the FoxH1-Mediated Wnt/β-catenin pathway.
abstract: The mechanisms underlying the growth inhibitory effect of Benzyl isothiocyanate (BITC) against breast cancer are still not fully understood. Therefore, we further investigated the mechanism in BITC triggering breast cancer. In the present study, we found that the overexpression of FOXH1 in breast cancers tissues and cells, and FOXH1 significantly promoted cell proliferation, invasion and tumorigenesis in vitro. FOXH1 significantly increased the expression levels of β-catenin, cyclinD1, and c-myc proteins in breast cancer cells. Furthermore, siβ-catenin reduced FOXH1 promotion of cell proliferation and invasion in breast cancer cells. Taken together, these results suggest that FOXH1 promoted breast cancer cell growth and invasion by potentiating the Wnt/β-catenin pathway, suggesting that FOXH1 may be a potential molecular target for breast cancer prevention and therapy. Furthermore, BITC treatment has remarkable effect on the expression level of FOXH1 and β-catenin mRNA and protein in MCF-7 cells, MDA-MB-231 cells and SUM 159 cells. BITC treatment has an obvious significance on transcriptional activity of FOXH1. Cell growth and invasion inhibition resulting from BITC exposure were significantly augmented by FoxH1 knockdown. In conclusion, the present study provides novel insights into the molecular circuitry of BITC-induced cell death involving FoxH1-mediated tumorigenesis. Thus, the present study provides a novel insight into the underlying mechanism of tumorigenesis in BITC triggering breast cancer, indicating the therapeutic potential of FOXH1 in the treatment of breast cancer.
authors.affiliation: Department of Pharmacy, West China Second University Hospital, Sichuan UniversityChengdu 610041, Sichuan, China; Evidence-Based Pharmacy Center, West China Second University Hospital, Sichuan UniversityChengdu 610041, Sichuan, China; Key Laboratory of Birth Defects and Related Diseases of Women and Children (Sichuan University), Ministry of EducationChengdu 610041, Sichuan, China.
authors.forename: Yantao
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Department of Pharmacy, West China Second University Hospital, Sichuan UniversityChengdu 610041, Sichuan, China; Evidence-Based Pharmacy Center, West China Second University Hospital, Sichuan UniversityChengdu 610041, Sichuan, China; Key Laboratory of Birth Defects and Related Diseases of Women and Children (Sichuan University), Ministry of EducationChengdu 610041, Sichuan, China.
authors.forename: Lingli
authors.initials: L
authors.lastname: Zhang
authors.affiliation: School of Medical Laboratory Science, Chengdu Medical College Chengdu 610041, Sichuan, China.
authors.forename: Yao
authors.initials: Y
authors.lastname: Meng
authors.affiliation: Department of Pharmacy, West China Second University Hospital, Sichuan UniversityChengdu 610041, Sichuan, China; Evidence-Based Pharmacy Center, West China Second University Hospital, Sichuan UniversityChengdu 610041, Sichuan, China; Key Laboratory of Birth Defects and Related Diseases of Women and Children (Sichuan University), Ministry of EducationChengdu 610041, Sichuan, China.
authors.forename: Liang
authors.initials: L
authors.lastname: Huang
keywords: Benzyl isothiocyanate; FoxH1; Wnt; tumorigenesis; β-catenin