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Sarsaparilla (Smilax Glabra Rhizome) extract inhibits migration and invasion of cancer cells by suppressing TGF-?1 pathway.

ABSTRACT: Sarsaparilla, also known as Smilax Glabra Rhizome (SGR), was shown to modulate immunity, protect against liver injury, lower blood glucose and suppress cancer. However, its effects on cancer cell adhesion, migration and invasion were unclear. In the present study, we found that the supernatant of water-soluble extract from SGR (SW) could promote adhesion, inhibit migration and invasion of HepG2, MDA-MB-231 and T24 cells in vitro, as well as suppress metastasis of MDA-MB-231 cells in vivo. Results of F-actin and vinculin dual staining showed the enhanced focal adhesion in SW-treated cells. Microarray analysis indicated a repression of TGF-?1 signaling by SW treatment, which was verified by real-time RT-PCR of TGF-?1-related genes and immunoblotting of TGFBR1 protein. SW was also shown to antagonize TGF-?1-promoted cell migration. Collectively, our study revealed a new antitumor function of Sarsaparilla in counteracting invasiveness of a subset of cancer cells by inhibiting TGF-?1 signaling.

SUBMITTER: She T

PROVIDER: S-EPMC4351248 | biostudies-literature | 2015

REPOSITORIES: biostudies-literature

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Sarsaparilla (Smilax Glabra Rhizome) extract inhibits migration and invasion of cancer cells by suppressing TGF-β1 pathway.

She Tiantian T Zhao Chuanke C Feng Junnan J Wang Lixin L Qu Like L Fang Ke K Cai Shaoqing S Shou Chengchao C

PloS one 20150305 3

Sarsaparilla, also known as Smilax Glabra Rhizome (SGR), was shown to modulate immunity, protect against liver injury, lower blood glucose and suppress cancer. However, its effects on cancer cell adhesion, migration and invasion were unclear. In the present study, we found that the supernatant of water-soluble extract from SGR (SW) could promote adhesion, inhibit migration and invasion of HepG2, MDA-MB-231 and T24 cells in vitro, as well as suppress metastasis of MDA-MB-231 cells in vivo. Result ...[more]

PMID: 25742000

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Project description:Dickkopf-1 (DKK1), an inhibitor of the most frequently impaired signaling pathway in hepatocellular carcinoma (HCC), the Wnt/beta-catenin pathway, seems to fulfill contradictory functions in the process of tumorigenesis, acting either as an oncogenic promoter of metastasis or as a tumor suppressor. Elevated serum levels of DKK1 have been reported in HCC; however, little is known about its functional significance. In the current study, we treated HepG2/C3A and PLC/PRF/5 with the recombinant protein DKK1. Cytotoxicity was first determined by the WST-8 assay. AFP expression was measured at both the mRNA and protein levels. Expression of the oncogenes MYC, CCND1, hTERT, and MDM2 and the tumor suppressor genes TP53, P21 and RB was assessed. Western blot analysis of non-phosphorylated ẞ-catenin and Sanger sequencing were performed to explain the functional differences between the two cell lines. Subsequently, inflammation, migration and invasion were evaluated by qPCR, ELISA, the Boyden chamber assay, zymography, and MMP-2 and MMP-9 western blot analysis. Knockdown of DKK1 and TGF-β1 were also performed. Our results suggest that DKK1 exerts an oncogenic effect on HepG2/C3A cell line by upregulating the expression of oncogenes and downregulating that of tumor suppressor genes, whereas the opposite effect was demonstrated in PLC/PRF/5 cells. This differential impact of DKK1 can be explained by the mutations that affect the canonical Wnt pathway that were detected in exon 3 of the CTNNB1 gene in the HepG2 cell line. We further confirmed that DKK1 promotes inflammation, tumor invasion and migration in both cell types. The canonical pathway was not responsible for the DKK1 proinvasive effect, as indicated by the active ẞ-catenin levels in the two cell lines upon DKK1 treatment. Interestingly, knockdown of TGF-β1 negatively affected the DKK1 proinvasive effect. Taken together, DKK1 appears to facilitate tumor invasion and migration through TGF- β1 by remodeling the tumor microenvironment and inducing inflammation. This finding endorses the relevance of TGF-β1 as a therapeutic target.

Dataset Information

Sarsaparilla (Smilax Glabra Rhizome) extract inhibits migration and invasion of cancer cells by suppressing TGF-?1 pathway.

Publications

Sarsaparilla (Smilax Glabra Rhizome) extract inhibits migration and invasion of cancer cells by suppressing TGF-β1 pathway.

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