Antiproliferative effects of the major tea polyphenol, (-)-epigallocatechin gallate and retinoic acid in cervical adenocarcinoma.
OBJECTIVE
To investigate the combined effect of the major tea polyphenol, (-)-epigallocatechin gallate (EGCG) and retinoic acid (RA) on cervical adenocarcinoma.


METHODS
Cell growth rate was examined after treatment for 4, 7 and 10 days with 0-100 microM EGCG and/or 1 microM RA in two cervical adenocarcinoma cell lines, HeLa and TMCC-1. The effect of EGCG treatment was examined for the induction of apoptosis by DNA ladder assay and caspase-3-related protease activity in cell lysate. Telomerase activity was detected by stretch PCR telomere extension assay. hTERT expression levels were quantified by a real-time PCR system.


RESULTS
Combining EGCG and RA increased the antiproliferative effect in adenocarcinoma cell lines, whereas EGCG or RA treatment alone caused a less sensitive response in these cells. Neither EGCG nor RA treatment alone affected apoptosis and telomerase activity. The combination treatment of EGCG and RA induced apoptosis and inhibited telomerase activity in adenocarcinoma cell lines. These results were consistent with those of an antiproliferative effect of EGCG and/or RA in cervical adenocarcinoma cells.


CONCLUSIONS
Our data suggest that EGCG and RA combined to prevent the carcinogenesis of cervical adenocarcinoma, induce apoptosis and inhibit telomerase activity. The treatments of combining EGCG and RA may be effective in preventing or treating cervical adenocarcinoma.
Department of Obstetrics and Gynecology, Faculty of Medicine, Saga University, 5-1-1, Nabeshima, Saga, 849-8501, Japan. yokoyam1@cc.saga-u.ac.jp
Msatoshi
M
Yokoyama
Mitsuyo
M
Noguchi
Yoshifumi
Y
Nakao
Makio
M
Ysunaga
Fumio
F
Yamasaki
Tsuyoshi
T
Iwasaka
D000230:Adenocarcinoma / Q000188:drug therapy* / Q000201:enzymology / Q000473:pathology; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D053148:Caspase 3 / Q000378:metabolism; D002392:Catechin / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D048708:Cell Growth Processes / Q000187:drug effects; D045744:Cell Line, Tumor; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D005260:Female; D006367:HeLa Cells; D006801:Humans; D019098:Telomerase / Q000378:metabolism; D014212:Tretinoin / Q000008:administration & dosage / Q000494:pharmacology*; D002583:Uterine Cervical Neoplasms / Q000188:drug therapy* / Q000201:enzymology / Q000473:pathology
D014212:Tretinoin; D002392:Catechin; C045651:epigallocatechin gallate; C509186:TERT protein, human; D019098:Telomerase; D053148:Caspase 3