Resveratrol-induced apoptosis and increased radiosensitivity in CD133-positive cells derived from atypical teratoid/rhabdoid tumor.
OBJECTIVE
CD133 has recently been proposed as a marker for cancer stem-like cells (CSC) in brain tumors. The aim of the present study was to investigate the possible role of resveratrol (RV) in radiosensitivity of CD133-positive/-negative cells derived from atypical teratoid/rhabdoid tumors (AT/RT-CD133(+/-)).


METHODS
AT/RT-CD133(+/-) were isolated and characterized by flow cytometry and quantitative real-time reverse transcription-polymerase chain reaction, and then treated with RV at different doses. Migratory ability, colony formation, apoptotic activity, and xenotransplantation were assessed for RV alone, ionizing radiation (IR) alone, and IR with RV conditions.


RESULTS
AT/RT-CD133(+) displayed enhanced self-renewal and highly coexpressed "stem cell" genes and drug-resistant genes, in addition to showing significant resistance to chemotherapeutic agents and radiotherapy as compared with CD133(-) cells. After treatment with 200 microM RV, the in vitro proliferation rates and in vivo tumor restoration abilities of ATRT-CD133(+) were dramatically inhibited. Importantly, treatment with 150 microM RV can effectively inhibit the expression of drug-resistant genes in AT/RT-CD133(+), and further facilitate to the differentiation of CD133(+) into CD133(-). In addition, treatment with 150 microM RV could significantly enhance the radiosensitivity and IR-mediated apoptosis in RV-treated ATRT-CD133(+/-). Kaplan-Meier survival analysis indicated that the mean survival rate of mice with ATRT-CD133(+) that were treated with IR could be significantly improved when IR was combined with 150 microM RV treatment.


CONCLUSIONS
AT/RT-CD133(+) exhibit CSC properties and are refractory to IR treatment. Our results suggest that RV treatment plays crucial roles in antiproliferative, proapoptotic, and radiosensitizing effects on treated-CD133(+/-); RV may therefore improve the clinical treatment of AT/RT.
Kao
Chung-Lan
CL
Institute of Clinical Medicine, National Yang-Ming University, Taipei, Taiwan.
Huang
Pin-I
PI
Tsai
Ping-Hsing
PH
Tsai
Ming-Long
ML
Lo
Jeng-Fan
JF
Lee
Yi-Yen
YY
Chen
Yann-Jang
YJ
Chen
Yi-Wei
YW
Chiou
Shih-Hwa
SH
D000071916:AC133 Antigen; D000818:Animals; D015703:Antigens, CD / Q000032:analysis; D000951:Antigens, Neoplasm / Q000032:analysis; D017209:Apoptosis / Q000187:drug effects*; D014408:Biomarkers, Tumor / Q000032:analysis; D049109:Cell Proliferation; D006023:Glycoproteins / Q000032:analysis; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D016513:Mice, SCID; D010455:Peptides / Q000032:analysis; D011836:Radiation Tolerance / Q000187:drug effects* / Q000235:genetics; D011838:Radiation-Sensitizing Agents / Q000627:therapeutic use*; D000077185:Resveratrol; D018335:Rhabdoid Tumor / Q000737:chemistry / Q000188:drug therapy / Q000473:pathology / Q000532:radiotherapy*; D013267:Stilbenes / Q000627:therapeutic use*; D013724:Teratoma / Q000737:chemistry / Q000188:drug therapy / Q000473:pathology / Q000532:radiotherapy*
D000071916:AC133 Antigen; D015703:Antigens, CD; D000951:Antigens, Neoplasm; D014408:Biomarkers, Tumor; D006023:Glycoproteins; C000606023:PROM1 protein, human; D010455:Peptides; C000606024:Prom1 protein, mouse; D011838:Radiation-Sensitizing Agents; D013267:Stilbenes; D000077185:Resveratrol