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

Abstract

Background Casticin expresses multiple anti‐cancer activities, whereas the effect of casticin on oral squamous cell carcinoma (OSCC) is still unclear. β‐catenin signaling plays a crucial role in the epithelial‐mesenchymal transition which is closely related to tumorigenesis. Herein, we aimed to study the functions of casticin on invasion and migration of OSCC, and clarify whether the effect of casticin on OSCC has a relationship with β‐catenin signaling. Methods Human OSCC cell lines UM1 and HSC‐3 were treated with different concentrations of casticin. The cell viability was evaluated by MTT and soft agar colony formation. Transwell assay and wound‐healing assay were performed to measure the ability of cell invasion and migration. The protein expression was assessed by Western blotting. Results Casticin displayed inhibitory activities of cell viability, invasion, and migration on OSCC cell lines. Meanwhile, casticin could reverse EMT process and inhibit the expression of β‐catenin in OSCC. Knock‐down or overexpression of β‐catenin could alter the effect of casticin on OSCC. Conclusions Casticin impaired invasion and migration of OSCC by inhibition of β‐catenin and reversal of EMT and could be a potential anti‐cancer bioactive agent.

Activation of PGK1 under hypoxic conditions promotes glycolysis and increases stem cell‑like properties and the epithelial‑mesenchymal transition in oral squamous cell carcinoma cells via the AKT signalling pathway

“…2D ). Since EMT is a key process in potentiating tumour migration and invasion ( 7 ), the role of hypoxia in the invasion and migration of OSCC cells was assessed by Transwell assays. Hypoxia was found to significantly enhance HN6 and HSC3 cell migration and invasion compared with normoxic cells ( Fig.…”

“…At present, surgery combined with radiotherapy and chemotherapy is the primary treatment option for oral cancer. However, the 5-year survival rate of patients with oral cancer has not significantly improved over the past decade ( 6 , 7 ). The invasive and metastatic ability of tumour cells is one of the main factors affecting the prognosis of patients ( 8 ).…”

An Overview of the Potential Antineoplastic Effects of Casticin

“…The overexpression of β-catenin induces proliferation, invasion and migratory activities in tumor cells, while its downmodulation can negatively regulate these tumorigenic processes. Additionally, casticin reversed epithelial-mesenchymal transition (EMT) in a dose-dependent manner [99]. In a second study, casticin inhibited cell viability by upregulating ROS and Ca2+ ions, decreasing ∆Ψm; activating caspase-3, -8 and -9 and upregulating AIF and cytochrome c. Casticin also has the ability to inhibit EMT transitioning, where epithelial cells become more migratory by losing their polarity and junctions.…”

“…It is characterized by increasing the expression of mesenchymal genes such as fibronectin, vimentin and N-cadherin and suppressing the expression of epithelial genes such as ocludin and E-cadherin [108][109][110][111][112][113][114][115]. It has been found that various concentrations of casticin can reverse the EMT process by increasing E-cadherin expression while inhibiting N-cadherin in oral squamous cell carcinoma (OSCC) UM1 cells [99], ovarian cancer SKOV3 cells [103] and liver cancer stem cells (LCSCs) derived from the SMMC-7721 cells [79]. After exposure to casticin, mRNA levels of Twist1 and N-cadherin decreased with the time progressed, most notably at 24 h in SKOV3 cells [103].…”

“…As more than 90% of cancer patients die due to persistent recurrence, metastasis and chemotherapy resistance, there is a need for studies to prevent or target metastasis [116][117][118][119][120][121][122]. Casticin significantly reduced the cell migration rate by 77.41% after 48 h of 5 µM compared to the control of DU145 cells [99] and inhibited cell migration by 93% after 24 h of 200 nM in human melanoma A375.S2 cancer cells [123]. In addition, MMP-2/-9 activities were inhibited in a concentration-and time-dependent manner in DU145 cells [124].…”