Evaluation of radiotherapy effect in resveratrol-treated medulloblastoma cancer stem-like cells.
OBJECTIVE
Resveratrol (RV), a natural polyphenol derived from red wine, recently showed the potential of anticancer and radiosensitizing effects. A recent study has suggested that the cancer stem cells (CSCs) may reflect the clinical refractory malignancy of brain tumors, including medulloblastoma (MB). The aim of the present study is to investigate the possible role of RV in radiosensitivity of MB cells and MB-associated CSCs.


METHODS
MB-associated CSCs were isolated and cultured by serum-free medium with basic fibroblast growth factor (bFGF) and epidermal growth factor (EGF). The parental MB cells and MB-CSCs were treated with RV in different concentrations and assessed for cell viability. The treatment includes RV alone, radiation alone, or radiation combined with RV.


RESULTS
MB-CSCs selected by serum-free medium with bFGF and EGF can form 3D spheroid formation and display enhanced self-renewal and highly co-expressed "stem cell" genes (Oct-4, Nanog, Nestin, and Musashi-1) as well as antiapoptotic genes (Bcl-2 and Bcl-xL). These MB-CSCs showed significant resistance to radiotherapy as compared to the parental MB cells. Importantly, 100 muM RV could effectively inhibit the proliferation of MB-CSCs and significantly enhance the radiosensitivity in RV-treated MB-CSCs.


CONCLUSIONS
Our data suggest that RV can effectively inhibit the proliferation and tumorigenicity of MB-CSCs and significantly synergistically enhance radiosensitivity in RV-treated MB-CSCs.
Lu
Kai-Hsi
KH
Institute of Microbiology and Immunology, National Yang-Ming University, Taipei, Taiwan.
Chen
Yi-Wei
YW
Tsai
Ping-Hsing
PH
Tsai
Ming-Long
ML
Lee
Yi-Yen
YY
Chiang
Chih-Yao
CY
Kao
Chung-Lan
CL
Chiou
Shih-Hwa
SH
Ku
Hung-Hai
HH
Lin
Chi-Hung
CH
Chen
Yann-Jang
YJ
D016588:Anticarcinogenic Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D049109:Cell Proliferation / Q000187:drug effects*; D002478:Cells, Cultured; D017024:Chemotherapy, Adjuvant; D006801:Humans; D007381:Intermediate Filament Proteins / Q000235:genetics; D008527:Medulloblastoma / Q000188:drug therapy* / Q000532:radiotherapy*; D014411:Neoplastic Stem Cells / Q000187:drug effects* / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000235:genetics; D064231:Nestin; D018714:Radiotherapy, Adjuvant; D000077185:Resveratrol; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013267:Stilbenes / Q000008:administration & dosage / Q000627:therapeutic use*; D051028:bcl-2-Associated X Protein / Q000235:genetics; D051020:bcl-X Protein / Q000235:genetics
D016588:Anticarcinogenic Agents; D007381:Intermediate Filament Proteins; C577484:NES protein, human; D009419:Nerve Tissue Proteins; D064231:Nestin; D013267:Stilbenes; D051028:bcl-2-Associated X Protein; D051020:bcl-X Protein; D000077185:Resveratrol