Inactivated Wnt signaling in resveratrol-treated epidermal squamous cancer cells and its biological implication

Abstract

Squamous cell carcinoma (SCC) is the most common epidermal malignancy, and Wnt/β-catenin signaling is frequently activated in SCC. Resveratrol prevents rodent epidermal carcinogenesis, while its effect on human epidermal cancer remains unknown. To address this issue, the impact of resveratrol on the growth and Wnt signaling of skin SCC Colo16 cells were investigated at the cellular and molecular biology levels by flow cytometry, immunocytochemistry, reverse transcription-polymerase chain reaction, western blotting and β-catenin-specific small interfering RNA (siRNA) transfection. Resveratrol (100 µM) suppressed cell growth and induced apoptosis in Colo16 cells. Wnt2 and its downstream genes were downregulated, which was accompanied by increased expression of the Wnt signaling inhibitor Axin2. Transfection with a β-catenin-specific siRNA did not affect cell growth but enhanced the resveratrol susceptibility of Colo16 transfectants. The present results suggest the inhibitory effects of resveratrol on epidermal SCCs and inactivation of Wnt signaling as one of the resveratrol-caused molecular events in Colo16 cells. β-catenin oriented siRNA is insufficient to induce cell crisis, implicating the presence of more critical cancer-associated element(s) as the target in Colo16 cells.

A Unique Panel of Patient-Derived Cutaneous Squamous Cell Carcinoma Cell Lines Provides a Preclinical Pathway for Therapeutic Testing

“…There are a number of publications using the UT-SCC HNSCC lines, which include five primary cSCC lines (UT-SCC-12A, 91, 105, 111, 118) and three metastatic cSCC lines (UT-SCC-7, 59A, 115) [13,14,15], but the characterisation of these lines has not been reported comprehensively. SRB-1 and SRB-12 cell lines were derived from a moderately well-differentiated cSCC [6,16,17], and Colo16 was developed from a metastatic cSCC arising in a chronic burn scar on the leg of a 59-year-old black female [18]; all three have subsequently been used in drug discovery studies [19,20,21,22,23,24,25,26,27]. A model of skin carcinogenesis has been developed using mutant Ras/Cdk4 transfection of normal keratinocytes [28,29]; however, HRas mutations are uncommon in human cSCC.…”

Regulation of Cell Signaling Pathways and miRNAs by Resveratrol in Different Cancers

“…Resveratrol can downregulate WNT2 and upregulate AXIN2 in Colo16 cells [ 27 ]. Furthermore, there was an earlier induction of apoptosis in resveratrol-treated β-catenin-silenced Colo16 cells [ 27 ].…”

“…Resveratrol can downregulate WNT2 and upregulate AXIN2 in Colo16 cells [ 27 ]. Furthermore, there was an earlier induction of apoptosis in resveratrol-treated β-catenin-silenced Colo16 cells [ 27 ]. Resveratrol dose-dependently decreased exogenously overexpressed Myc-tagged TCF4 protein in colorectal cancer cells [ 28 ] and increased TCF4 phosphorylation through ERK- and p38-MAPK-modulated pathways.…”

Resveratrol, cancer and cancer stem cells: A review on past to future

“…(2015) Glioblastoma patient derived stem cells (GBM2, GBM7, G144, G179, G166, GliNS2, GBM04) Wnt and EMT activator mediated GSC cell proliferation ↓ Cell mortality ↑ Cell motility ↑ Cilibrasi et al. (2017) Squamous cell carcinoma cell line (Colo 16 cells) RSV (100 μM) exhibited Wnt ↓ leading to Cell growth ↓ Apoptosis ↑ Transfection with β-catenin-specific siRNA enhanced RSV susceptibility Liu et al. (2017) GC-MSCs derived from the gastric adenocarcinoma patient tissues RSV reversed the progress of EMT Metastasis ↓ Wnt/β-catenin pathway proteins ↓ Yin et al.…”