Casticin inhibits the epithelial-mesenchymal transition in ovarian carcinoma via the hedgehog signaling pathway

Abstract

Abstract. Casticin inhibits migration, invasion and induced apoptosis in numerous cancer cells; however, the Hedgehog (Hh) signaling pathway is a key factor in the epithelial-mesenchymal transition (EMT). The present study aimed to assess whether casticin affects the expression of members of the Hh signaling pathway and EMT effectors in ovarian carcinoma. The ovarian cancer SKOV3 cell line was incubated in the presence of various concentrations of casticin or cyclopamine. Next, the expression levels of the main Hh signaling effector glioma-associated oncogene-1 (Gli-1) and EMT-associated factors [Twist-related protein 1 (Twist1), E-cadherin and N-cadherin] were determined by western blotting and reverse transcription-quantitative polymerase chain reaction. Cell proliferation and growth were assessed using MTT and soft agar assays; cell migration and invasion was evaluated using an in vitro migration assay and a transwell invasion assay, respectively. Compared with control group values, Gli-1, Twist1 and N-cadherin expression levels were reduced, whereas E-cadherin levels were increased in the casticin-and cyclopamine-treated groups. Incubation with casticin or cyclopamine resulted in markedly reduced SKOV3 cell viability, migration and invasion, in a dose-dependent manner. To the best of our knowledge, the findings of the present study indicated for first time that casticin may inhibit EMT via Hh signaling in vitro, reducing the migratory ability of ovarian cancer cells.

Casticin inhibits invasion and proliferation via downregulation of β‐catenin and reversion of EMT in oral squamous cell carcinoma

“…When EMT occurs, the expression of E‐cadherin reduced while N‐cadherin expression increased. Reports had demonstrated that casticin‐inhibited EMT in ovarian carcinoma and hepatocellular carcinoma . In the present study, we demonstrated that casticin induced the expression of E‐cadherin but inhibited the expression of N‐cadherin through Western blotting, which indicates that the inhibition of cell invasion and migration by casticin may be companies with the suppression of EMT.…”

Identification of new hypoxia‐regulated epithelial‐mesenchymal transition marker genes labeled by H3K4 acetylation

“…Among the new EMT marker genes, GLI1 and SMO are two genes belong to the Hedgehog pathway. Increasing evidence suggests that Hedgehog‐GLI1 signaling plays an important role in EMT of several tumor types, including ovarian cancer, gastric cancer, and pancreatic cancer, where GLI1 expression is essential for cancer cell survival and facilitates the migration and invasion of cancer cells by promoting the EMT process . Although these two biomarkers need to be confirmed in larger cohorts, our results show that both GLI1 and SMO tend to be upregulated in metastatic tumors in comparison with primary tumors, and cooverexpression of GIL1/SMO is associated with HNSCC metastasis, indicating the importance of the Hedgehog pathway to contribute to hypoxia‐induced EMT and metastasis, and the prognostic significance of GLI1/SMO in HNSCC patients.…”

“…Among the new EMT marker genes, GLI1 and SMO are two genes belong to the Hedgehog pathway. Increasing evidence suggests that Hedgehog-GLI1 signaling plays an important role in EMT of several tumor types, including ovarian cancer,43 gastric cancer,44 and pancreatic cancer,…”

An Overview of the Potential Antineoplastic Effects of Casticin

“…Glioma-associated oncogene-1 (Gli-1) and EMT-associated hedgehog factors, including Twist1 levels, were also reduced. The hedgehog signaling pathway transforms key information necessary for cell differentiation [102]. In this way, casticin can inhibit cell invasion, migration and viability in human ovarian cancer cell lines.…”