Suppression of telomerase activity and arrest at G1 phase in human cervical cancer HeLa cells by all-trans retinoic acid.
Of all neoplasms found in women, cervical cancer has the third highest incidence and causes the fourth most deaths. All-trans retinoic acid (ATRA) may be with chemopreventive potential on cervical cancer, but the mechanisms underlying is not clear. To investigate the mechanisms, human cervical cancer HeLa cells were treated with ATRA for 1, 2, 3, or 4 days in vitro. We found that ATRA inhibited the growth of HeLa cells in a dose-dependent manner at the concentrations from 0.3 to 9.6 mumol/L. Flow cytometric analysis showed that HeLa cells were arrested at G0/G1 phase by ATRA, and the aneuploidy was found when cells were treated for 4 days, which is the first report that ATRA causes aneuploid cycle in HeLa cells. The expression of human telomerase catalytic subunit messenger RNA was decreased remarkably by ATRA. These findings suggested that the inhibition of telomerase activity and arrest of cells at G0/G1 phase might be the key steps through which ATRA inhibits the proliferation of HeLa cells. Our results provide a possible mechanistic explanation for the growth inhibitory effect of ATRA on HeLa cells. Therefore, retinoids may have therapeutic potential to complement current treatments of cervical cancers.
Guo
J M
JM
School of Medicine, Ningbo University, Ningbo 315211, China. junmingguo@yahoo.com
Xiao
B X
BX
Kang
G Z
GZ
Liu
D H
DH
Chen
H
H
Zhang
S
S
Zhang
X N
XN
D017209:Apoptosis / Q000187:drug effects; D014408:Biomarkers, Tumor / Q000032:analysis; D002453:Cell Cycle / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D016193:G1 Phase / Q000187:drug effects* / Q000502:physiology; D006367:HeLa Cells / Q000187:drug effects; D006801:Humans; D066298:In Vitro Techniques; D011336:Probability; D012333:RNA, Messenger / Q000032:analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012680:Sensitivity and Specificity; D019098:Telomerase / Q000187:drug effects / Q000378:metabolism*; D014212:Tretinoin / Q000494:pharmacology*; D014407:Tumor Cells, Cultured; D002583:Uterine Cervical Neoplasms / Q000188:drug therapy / Q000473:pathology
D014408:Biomarkers, Tumor; D012333:RNA, Messenger; D014212:Tretinoin; D019098:Telomerase