Anticancer effect of aloe-emodin on cervical cancer cells involves G2/M arrest and induction of differentiation.
OBJECTIVE
The aim of this study was to investigate the effects of aloe-emodin, a natural compound from the root and rhizome of Rheum palmatum, on the growth of human cervical cancer cells, HeLa.


METHODS
HeLa cells were treated with various concentrations of aloe-emodin for 1-5 d, and cell growth was measured by 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyl tetrazolium bromide assay. The long-term growth effect was investigated by crystal violet assay. The distributions of the cell cycle and apoptosis were analyzed by flow cytometry. The alkaline phosphatase (ALP) activity was analyzed by a chemical analyzer. Finally, Western blotting was used to indicate the abundant changes of protein kinase C (PKC), c-myc, cyclins, cyclin-dependent kinases (CDK), and proliferating cell nuclear antigen (PCNA).


RESULTS
Aloe-emodin inhibited the growth of HeLa cells in a dose-dependent manner at concentrations ranging between 2.5 and 40 micromol/L. The flow cytometric analysis showed that HeLa cells were arrested at the G2/M phase. This effect was associated with the decrease in cyclin A and CDK2, and the increase in cyclin B1 and CDK1. More importantly, the ALP activity was found to be increased by aloe-emodin treatment, and accompanied by the inhibition of PCNA expression. In addition, aloe-emodin suppressed the expression of PKCalpha and c-myc.


CONCLUSIONS
These findings provide a possible mechanistic explanation for the growth inhibitory effect of aloe-emodin on HeLa, which includes cell cycle arrest and inducing differentiation.
Guo
Jun-ming
JM
Ningbo University School of Medicine, Ningbo 315211, China. junmingguo@yahoo.com
Xiao
Bing-xiu
BX
Liu
Qiong
Q
Zhang
Shun
S
Liu
Dong-hai
DH
Gong
Zhao-hui
ZH
D000880:Anthraquinones / Q000494:pharmacology*; D002454:Cell Differentiation / Q000187:drug effects*; D002455:Cell Division / Q000187:drug effects*; D005260:Female; D016195:G2 Phase / Q000187:drug effects*; D006367:HeLa Cells; D006801:Humans; D002583:Uterine Cervical Neoplasms / Q000473:pathology*
D000880:Anthraquinones; C518327:aloe emodin