Avicularin inhibits cell proliferation and induces cell apoptosis in cutaneous squamous cell carcinoma

Abstract

Avicularin (AL), quercetin-3-α-L-arabinofur anoside, has various pharmacological properties such as anticancer and anti-infective effects. However, the potential molecular mechanism via which AL exerts its anticancer activity is not fully understood. Cutaneous squamous cell carcinoma (CSCC) is the second most common skin cancer, where metastasis has resulted in in effective clinical treatments. The aim of the present in vitro study was to investigate the anticancer effects and underlying mechanism of AL on human CSCC. The present results suggested that AL dose-dependently inhibited SCC13 cell viability and induced apoptosis. In addition, the present results suggested that AL induced apoptosis via repression of the mitogen-activated protein kinase kinase (MEK)/NF-κB signal pathway, thereby affecting the expression of apoptosis-related genes. Bax expression level was increased, while Bcl-2 expression level was decreased in SCC13 cells following AL treatment. In addition, the MEK/NF-κB signaling pathway-related genes p-MEK and phosphorylated-p65 were also decreased. The present results suggested that AL treatment increased the expression level of E-cadherin, but decreased the expression levels of N-cadherin, matrix metalloproteinase (MMP)-9 and vimentin in SCC13 cells. Collectively, the present results suggested that AL may have an anti-CSCC effect by inhibiting cell viability, inducing apoptosis and inhibiting epithelial-mesenchymal transition (EMT) of CSCC cells. The mechanism of these anti-CSCC effects was suggested to be via the regulation of apoptosis-related genes and EMT-related genes, and the inhibition of the MEK/NF-κB signaling pathway. Materials and methods Cell culture and treatment. DMEM (Gibco; Thermo Fisher Scientific, Inc) with 10% FBS (Gemini Bio-Products, Inc.), 10 U/ml penicillin-G and 10 mg/ml streptomycin (Gemini

Extracts of Spiraea hypericifolia L. and Spiraea crenata L.: The Phenolic Profile and Biological Activities

“…This flavonoid is one of the major components in our samples of the S. crenata extract. Another study has revealed that avicularin suppresses the viability of SCC13 skin squamous cell carcinoma cultured cells, by inducing apoptosis and inhibiting epithelial–mesenchymal transition [ 33 ]. It has been proposed that the mechanism of these effects against SCC13 cells is the modulation of genes related to apoptosis and epithelial–mesenchymal transition, as well as inhibition of the MEK–NF-κB signaling pathway.…”

A tEMTing target? Clinical and experimental evidence for epithelial-mesenchymal transition in the progression of cutaneous squamous cell carcinoma (a scoping systematic review)

“…Interestingly, inhibition of RhoA, a small GTPase involved in integrin and cell skeletal signalling, had the opposite effect of all previously discussed drugs and in fact promoted EMT [ 151 ]. Additionally, proof of concept studies using several natural compounds have reported modulation of EMT markers and properties in cSCC cell lines [ 112 , 149 , 152 , 153 ]. However, these studies lack proper validation of their targets, an in-depth assessment of potential off-target activities, and consequently an understanding for the signalling pathways modulated.…”

Bioactive Ingredients in K. pinnata Extract and Synergistic Effects of Combined K. pinnata and Metformin Preparations on Antioxidant Activities in Diabetic and Non-Diabetic Skeletal Muscle Cells

“…Lee et al demonstrated that avicularin possesses OH radical scavenging capacities [ 23 ]. Oxidative damage can be reduced and kept to a minimum by reducing hydroxyl radicals, which may, in turn, allow cell growth due to reduced inflammation caused by stress [ 24 ]. Although we did not investigate the effect of avicularin alone in our previous study that reported an increase in inflammatory markers, it may be due to the combined phytochemicals in the K. pinnata extract [ 14 ].…”

“…Like many of the other polyphenols previously mentioned, avicularin may offer help to type II diabetic patients. Studies have shown that avicularin can decrease the progression of type II diabetes by reducing levels of fasting blood glucose, triglycerides, and low-density lipoprotein cholesterol, improving β-cell function, and suppressing hepatic steatosis [ 24 , 25 ]. Kaempferol, another flavonoid found in K. pinnata , was shown to regulate concentrations of glucose within cells [ 26 ].…”