Genistein inhibits human papillary thyroid cancer cell detachment, invasion and metastasis

Abstract

Papillary thyroid carcinoma (PTC) is the most commonly diagnosed endocrine cancer, and those with BRAFV600E mutation have high recurrence rate and less favorable clinical behavior. Genistein having anti-carcinoma effects in various types of carcinomas as an estrogen analog, but the mechanism of Genistein in the progression of PTC remains unknown. Genistein significantly inhibits the proliferation and the invasion (P < 0.01), and the apoptosis (P < 0.001) of all tumor cell lines, which was probably due to the inducing of the arrest in G2/M phase of the cell cycle (P < 0.001). The anti-proliferation and apoptosis inducing effects are more obvious in BCPAP, IHH4 cell lines harboring BRAFV600E mutation. Genistein significantly decreased the invasion of PTC cell lines and partially reverses epithelial mesenchymal transition in PTC cell lines. Functional study indicated that small interfering RNA (siRNA) knockdown of β-catenin significantly reverses the effect of genistein on EMT at protein levels. In conclusion, for the first time, our study suggested that genistein has anticarcinoma effect for PTC patients in the range of 2.5 and 80 μg/ml in thyroid carcinoma cells, which was probably through cytoplasmic translocation of β-catenin. Further study will be needed to determine whether genistein could be used in clinical trial of high-risk PTC.

Oncogenic Mutation BRAF V600E Changes Phenotypic Behavior of THLE-2 Liver Cells through Alteration of Gene Expression

“…Deregulated activation of the BRAF V600E-dependent MAPK/ERK effectors is best recognized in the mechanisms underlying melanoma genesis and the growth of papillary thyroid cancer [32,55,56]. A predominantly similar phenotype is caused by the V600E mutation, including enhanced invasion, proliferation, and metastasis [32,55,56]. Our studies showed a significant similarity of the influence of BRAF V600E on the characteristics of THLE-2 cells, which may indicate a strong invasive and migration effect of this mutation in the liver tissue.…”

“…Constant activation of the MAPK/ERK pathway promotes cell migration, proliferation, and the tumor microenvironment [54]. Deregulated activation of the BRAF V600E-dependent MAPK/ERK effectors is best recognized in the mechanisms underlying melanoma genesis and the growth of papillary thyroid cancer [32,55,56]. A predominantly similar phenotype is caused by the V600E mutation, including enhanced invasion, proliferation, and metastasis [32,55,56].…”

ZHX2 inhibits thyroid cancer metastasis through transcriptional inhibition of S100A14

“…The human ATC cell lines 8305C (RRID: CVCL_1053), BHT101 (RRID: CVCL_1085) and KMH-2 (RRID: CVCL_S641) were kindly provided by the Stem Cell Bank, Chinese Academy of Sciences (Shanghai, China). The PTC cell line BHP10-3 (RRID: CVCL_6278) was obtained from Qilu Hospital of Shandong University [ 23 ]. All cell lines that were authenticated using STR profiling within the last 3 years were included.…”

Herbal Active Ingredients: An Emerging Potential for the Prevention and Treatment of Papillary Thyroid Carcinoma

“…Genistein is the main active ingredient of Leguminosae. is isoflavone inhibits the invasion and metastasis of the PTC-derived BHP10-3 cell (with RET/PTC 1 rearrangement), BCPAP, and IHH4 (with BRAF V600E mutation) by inhibiting β-catenin and EMT [46]. However, genistein upregulates most thyroid transcript signals, except for thyroid peroxidase, in zebrafish embryos, thereby indicating potential disruptions [105].…”