Growth inhibition and induction of differentiation by panaxydol in rat C6 glioma cells.
OBJECTIVE
Panaxydol is a naturally occurring non-peptidyl small molecule isolated from the lipophilic fractions of Panax notoginseng, a well-known Chinese traditional medicine. In this study, we aimed to investigate the effects of panaxydol on growth inhibition and its mechanisms in C6 rat glioma cells.


METHODS
The effects of panaxydol on cell proliferation, morphologic changes, glial fibrillary acidic protein (GFAP) expression and cell cycle regulation in rat C6 cells were evaluated using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay, hematoxylin and eosin (HE) staining, immunocytochemistry, flow cytometric analysis and Western blot respectively.


RESULTS
Panaxydol markedly inhibited the proliferation of C6 cells in a dose-dependent manner with IC50 of 39.5 +/- 2.3 microM. In addition, the cell morphologic changes and increased expression of GFAP in C6 cells in the presence of panaxydol implied a cellular differentiation. Flow cytometric analysis revealed that panaxydol-treated cells accumulated in G0/G1 phase with a marked decrease in the number of C6 cells at S phase. Western blot analysis demonstrated that panaxydol resulted in an increase in the protein expression of p27 in C6 cells as early as 3 hours after treatment consistent with the differentiation response, but protein expression of p53, p21, p16 and pRb remained unchanged.


CONCLUSIONS
These findings suggest that panaxydol inhibits the proliferation of C6 cells via G0/G1 cell cycle arrest in association with induction of p27 expression and differentiation.
Hai
Jian
J
Department of Neurosurgery, Tongji Hospital, Tongji University, Shanghai, China. haijiandoc@yahoo.com.cn
Lin
Qi
Q
Lu
Yang
Y
Yi
Jing
J
Zhang
Hao
H
D000818:Animals; D002453:Cell Cycle / Q000187:drug effects; D002454:Cell Differentiation / Q000187:drug effects*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D048429:Cell Size / Q000187:drug effects; D053280:Diynes / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004365:Drugs, Chinese Herbal / Q000494:pharmacology*; D005233:Fatty Alcohols / Q000494:pharmacology*; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D005910:Glioma / Q000473:pathology / Q000503:physiopathology; D018809:Proliferating Cell Nuclear Antigen / Q000378:metabolism; D051381:Rats; D013778:Tetrazolium Salts; D013844:Thiazoles; D013997:Time Factors
D053280:Diynes; D004365:Drugs, Chinese Herbal; D005233:Fatty Alcohols; D005904:Glial Fibrillary Acidic Protein; D018809:Proliferating Cell Nuclear Antigen; D013778:Tetrazolium Salts; D013844:Thiazoles; C413374:p27 antigen; C055778:panaxydol; C022616:thiazolyl blue