Anti-tumor effect of rutin on human neuroblastoma cell lines through inducing G2/M cell cycle arrest and promoting apoptosis.
OBJECTIVE
To further investigate the antineuroblastoma effect of rutin which is a type of flavonoid.


METHODS
The antiproliferation of rutin in human neuroblastoma cells LAN-5 were detected by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Chemotaxis of LAN-5 cells was assessed using transwell migration chambers and scratch wound migration assay. The cell cycle arrest and apoptosis in a dose-dependent manner was measured by flow cytometric and fluorescent microscopy analyses. The apoptosis-related proteins BAX and BCL2 as well as MYCN mRNA express were determined by RT-PCR analysis. Secreted TNF- α level were determined using specific enzyme-linked immunosorbent assay kits.


RESULTS
Rutin significantly inhibited the growth of LAN-5 cells and chemotactic ability. Flow cytometric analysis revealed that rutin induced G2/M arrest in the cell cycle progression and induced cell apoptosis. The RT-PCR showed that rutin could decrease BCL2 expression and BCL2/BAX ratio. In the meantime, the MYCN mRNA level and the secretion of TNF- α were inhibited.


CONCLUSIONS
These results suggest that rutin produces obvious antineuroblastoma effects via induced G2/M arrest in the cell cycle progression and induced cell apoptosis as well as regulating the expression of gene related to apoptosis and so on. It supports the viability of developing rutin as a novel therapeutic prodrug for neuroblastoma treatment, as well as providing a new path on anticancer effect of Chinese traditional drug.
Beijing Key Laboratory for Aging and Geriatrics, Institute of Geriatrics, General Hospital of Chinese PLA, Beijing, China.
Hongyan
H
Chen
National Institute of Occupational Health and Poison Control, Chinese Center for Disease Control and Prevention, Beijing, China.
Qing
Q
Miao
Beijing Key Laboratory for Aging and Geriatrics, Institute of Geriatrics, General Hospital of Chinese PLA, Beijing, China.
Miao
M
Geng
Beijing Key Laboratory for Aging and Geriatrics, Institute of Geriatrics, General Hospital of Chinese PLA, Beijing, China.
Jing
J
Liu
Beijing Key Laboratory for Aging and Geriatrics, Institute of Geriatrics, General Hospital of Chinese PLA, Beijing, China.
Yazhuo
Y
Hu
Beijing Key Laboratory for Aging and Geriatrics, Institute of Geriatrics, General Hospital of Chinese PLA, Beijing, China.
Lei
L
Tian
Beijing Key Laboratory for Aging and Geriatrics, Institute of Geriatrics, General Hospital of Chinese PLA, Beijing, China.
Jingkun
J
Pan
Minzu University of China, Beijing, China.
Yi
Y
Yang
D017209:Apoptosis / Q000187:drug effects* / Q000235:genetics; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects / Q000235:genetics; D059565:G2 Phase Cell Cycle Checkpoints / Q000187:drug effects* / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects / Q000235:genetics; D006801:Humans; D059566:M Phase Cell Cycle Checkpoints / Q000187:drug effects* / Q000235:genetics; D000071447:N-Myc Proto-Oncogene Protein; D009447:Neuroblastoma / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D009687:Nuclear Proteins / Q000096:biosynthesis / Q000235:genetics; D015513:Oncogene Proteins / Q000096:biosynthesis / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012431:Rutin; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism; D051028:bcl-2-Associated X Protein / Q000096:biosynthesis / Q000235:genetics
C494826:BAX protein, human; C459801:MYCN protein, human; D000071447:N-Myc Proto-Oncogene Protein; D009687:Nuclear Proteins; D015513:Oncogene Proteins; D014409:Tumor Necrosis Factor-alpha; D051028:bcl-2-Associated X Protein; D012431:Rutin