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Baicalein suppresses metastasis of breast cancer cells by inhibiting EMT via downregulation of SATB1 and Wnt/β-catenin pathway.
Drug Des Devel Ther. 2016; 10:1419-41.DD

Abstract

BACKGROUND

The 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.

METHODS

MTT 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.

RESULTS

Our 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.

CONCLUSION

Our 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.

Authors+Show Affiliations

Department of Oncology, the Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, People's Republic of China.Department of Oncology, the Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, People's Republic of China.Department of Oncology, the Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, People's Republic of China.Department of Oncology, the Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, People's Republic of China.Department of Oncology, the Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, People's Republic of China.Department of Oncology, Institute of Health, China North Industries Group Corporation, Xi'an, Shaanxi, People's Republic of China.Department of Thoracic Surgery, the Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, People's Republic of China.Department of Oncology, the Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, People's Republic of China.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

27143851

Citation

Ma, Xingcong, et al. "Baicalein Suppresses Metastasis of Breast Cancer Cells By Inhibiting EMT Via Downregulation of SATB1 and Wnt/β-catenin Pathway." Drug Design, Development and Therapy, vol. 10, 2016, pp. 1419-41.
Ma X, Yan W, Dai Z, et al. Baicalein suppresses metastasis of breast cancer cells by inhibiting EMT via downregulation of SATB1 and Wnt/β-catenin pathway. Drug Des Devel Ther. 2016;10:1419-41.
Ma, X., Yan, W., Dai, Z., Gao, X., Ma, Y., Xu, Q., Jiang, J., & Zhang, S. (2016). Baicalein suppresses metastasis of breast cancer cells by inhibiting EMT via downregulation of SATB1 and Wnt/β-catenin pathway. Drug Design, Development and Therapy, 10, 1419-41. https://doi.org/10.2147/DDDT.S102541
Ma X, et al. Baicalein Suppresses Metastasis of Breast Cancer Cells By Inhibiting EMT Via Downregulation of SATB1 and Wnt/β-catenin Pathway. Drug Des Devel Ther. 2016;10:1419-41. PubMed PMID: 27143851.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Baicalein suppresses metastasis of breast cancer cells by inhibiting EMT via downregulation of SATB1 and Wnt/β-catenin pathway. AU - Ma,Xingcong, AU - Yan,Wanjun, AU - Dai,Zhijun, AU - Gao,Xiaoyan, AU - Ma,Yinan, AU - Xu,Quntao, AU - Jiang,Jiantao, AU - Zhang,Shuqun, Y1 - 2016/04/18/ PY - 2016/5/5/entrez PY - 2016/5/5/pubmed PY - 2016/12/31/medline KW - EMT KW - SATB1 KW - Wnt/β-catenin pathway KW - baicalein KW - breast cancer KW - metastasis SP - 1419 EP - 41 JF - Drug design, development and therapy JO - Drug Des Devel Ther VL - 10 N2 - BACKGROUND: The 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. METHODS: MTT 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. RESULTS: Our 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. CONCLUSION: Our 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. SN - 1177-8881 UR - https://www.unboundmedicine.com/medline/citation/27143851/Baicalein_suppresses_metastasis_of_breast_cancer_cells_by_inhibiting_EMT_via_downregulation_of_SATB1_and_Wnt/β_catenin_pathway_ L2 - https://dx.doi.org/10.2147/DDDT.S102541 DB - PRIME DP - Unbound Medicine ER -