Baicalein suppresses metastasis of breast cancer cells by inhibiting EMT via downregulation of SATB1 and Wnt/β-catenin pathway

Abstract

BackgroundThe flavonoid baicalein, a historically used Chinese herbal medicine, shows a wide range of biological and pharmaceutical effects, among which its potent antitumor activity has raised great interest in recent years. However, the molecular mechanism involved in the antimetastatic effect of baicalein remains poorly understood. This study aimed to verify the inhibitory effects of baicalein on metastasis of MDA-MB-231 human breast cancer cells both in vitro and in vivo, as well as to investigate the related mechanisms.MethodsMTT assay was used to examine the inhibition of baicalein on proliferation of MDA-MB-231 cells. Wound healing assay and the in vitro invasion assay was carried out to investigate the effects of baicalein on migration and invasion of MDA-MB-231 cells, respectively. In order to explore the effects of baicalein on tumor metastasis in vivo, xenograft nude mouse model of MDA-MB-231 cells was established. Animals were randomly divided into four groups (control, therapy group, and low-dose and high-dose prevention group, n=6), and treated with baicalein as designed. Following sacrifice, their lungs and livers were collected to examine the presence of metastases. qRT-PCR and Western blot were performed to study the effects of baicalein on expression of SATB1, EMT-related molecules, and Wnt/β-catenin signaling components of MDA-MB-231 cells as well as the metastatic tissue. Effects of baicalein on the expression of target proteins in vivo were also analyzed by immunohistochemistry.ResultsOur results indicated that baicalein suppressed proliferation, migration, and invasion of MDA-MB-231 cells in a time- and dose-dependent manner. Based on assays carried out in xenograft nude mouse model, we found that baicalein inhibited tumor metastasis in vivo. Furthermore, baicalein significantly decreased the expression of SATB1 in MDA-MB-231 cells. It suppressed the expression of vimentin and SNAIL while enhancing the expression of E-cadherin. Baicalein also downregulated the expression of Wnt1 and β-catenin proteins and transcription level of Wnt/β-catenin-targeted genes.ConclusionOur results demonstrate that baicalein has the potential to suppress breast cancer metastasis, possibly by inhibition of EMT, which may be attributed to downregulation of both SATB1 and the Wnt/β-catenin pathway. Taken together, baicalein may serve as a promising drug for metastasis treatment of breast cancer.

Epithelial‐mesenchymal transition inducer Snail1 and invasive potential of intraductal breast cancer

“…Most recent studies suggest that Snail1 suppression can reduce invasive propensity of breast cancer cells . Moreover, some drugs and anti‐tumor agents have been reported to inhibit EMT by down‐regulation of Snail1 signaling pathway, which results in anti‐metastatic effect . Those findings and our results support the idea that Snail1 and upstream regulators of its expression and activity could be the logical therapeutic targets for suppressing the development of invasive breast cancer …”

The Fascinating Effects of Baicalein on Cancer: A Review

“…This study provided evidence for using baicalein as a promising agent in the treatment of metastasis in patients with breast cancer. The molecular mechanism of baicalein works via inhibition of epithelial-to-mesenchymal transition (EMT) and downregulation of special AT-rich sequence-binding protein-1 (SATB1) and Wnt/β-catenin pathways [10]. Consistent with the results of a former study by Ma et al, Gao et al also reported that baicalein inhibited the proliferation, migration, and invasiveness of MDA-MB-231 cells by suppressing the expression of SATB1.…”

“…Baicalein is a flavone and an active ingredient in the traditional herb, Huang Qin. There is an accumulating amount of evidence that demonstrates baicalein’s role in treating and preventing various types of cancer [9,10,11,12,13,14,15]. In this review, we explored its chemical structure, properties, and possible biological mechanisms through which it acts.…”

Baicalein Inhibits Epithelial to Mesenchymal Transition via Downregulation of Cyr61 and LOXL-2 in MDA-MB231 Breast Cancer Cells

“…Akt is frequently activated in various cancers and plays a critical role in the induction of TGFβ and EGF-dependent EMT (Bakin et al, 2000; Julien et al, 2007). Akt can also phosphorylate IKKα to increase Snail expression and induce the EMT (Ma et al, 2016). …”