Casticin inhibits epithelial-mesenchymal transition of liver cancer stem cells of the SMMC-7721 cell line through downregulating Twist.
The existence of cancer stem cells (CSCs) is central to the pathogenesis and therapeutic target of human hepatocellular carcinoma. The aim of this study was to investigate the effects of casticin on epithelial-mesenchymal transition (EMT) of liver cancer stem cells (LCSCs) derived from the SMMC-7721 cell line. Our results demonstrated that CD133+sphere-forming cells (SFCs) sorted from the SMMC-7721 cell line not only possessed a higher capacity to form tumor spheroidsin vitro, but also had a greater potential to form tumors when implanted in Balb/c-nu mice, indicating that CD133+SFCs possessed similar traits to LCSCs. Casticin increased the expression levels of E-cadherin and decreased those of N-cadherin in LCSCs. Treatment of LCSCs with casticin for 48 h also decreased the levels of the EMT-associated transcription factor, Twist. Overexpression of Twist attenuated the casticin-induced regulation of E-cadherin and N-cadherin protein expression, as well as the EMT capacity of LCSCs. In conclusion, CD133+SFCs of the SMMC-7721 cell line may represent a subpopulation of LCSCs with the characteristics of EMT. Furthermore, casticin targeted LCSCs through the inhibition of EMT by downregulating Twist.
Department of Oncology, The First Affiliated Hospital of University of South China, Hengyang, Hunan 421001, P.R. China.
Meng
M
He
Laboratory of Medicine Engineering, Medical College, Hunan Normal University, Changsha, Hunan 410013, P.R. China.
Xiao-Cheng
XC
Cao
Department of Oncology, The First Affiliated Hospital of University of South China, Hengyang, Hunan 421001, P.R. China.
Gui-Cheng
GC
He
Laboratory of Medicine Engineering, Medical College, Hunan Normal University, Changsha, Hunan 410013, P.R. China.
Xi-Feng
XF
Sheng
Department of Oncology, The First Affiliated Hospital of University of South China, Hengyang, Hunan 421001, P.R. China.
Xiao-Hong
XH
Ai
Department of Oncology, The First Affiliated Hospital of University of South China, Hengyang, Hunan 421001, P.R. China.
You-Hua
YH
Wu
Twist; casticin; epithelial-mesenchymal transition; hepatocellular carcinoma