Induction of apoptosis and inhibition of telomerase activity by arsenic trioxide (As2O3) in endometrial carcinoma cells.
OBJECTIVE
To examine the effects of arsenic trioxide (As2O3) on human endometrial carcinoma cell lines with respect to cytotoxicity and the induction of apoptosis and telomerase expression in vitro.


METHODS
Four endometrial carcinoma cell lines (Ishikawa, ECC-1, RL-95-2 and Hec-1B) were treated with increasing concentrations of As2O3.


RESULTS
As2O3 inhibited proliferation of all cell lines in a concentration and time-dependent manner (IC50 range of 3-7 microM). Coincident with the inhibition of growth, As2O3 also induced apoptosis in all cell lines as measured by the time-dependent increase in M30 antibody fluorescence (binds a caspase-cleaved epitope of cytokeratin 18) detected by flow cytometry, and reduced telomerase activity by decreasing the hTERT mRNA expression.


CONCLUSIONS
As2O3 may exert anti-tumor effects through the induction of the apoptosis pathway and telomerase and hTERT may play an important role in the anti-apoptotic effects which are observed when endometrial cancer cells are treated in vitro with As2O3.
Zhou
Chunxiao
C
Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, University of North Carolina at Chapel Hill, CB # 7570 MacNider Building, Chapel Hill, NC 27599-7570, USA.
Boggess
John F
JF
Bae-Jump
Victoria
V
Gehrig
Paola A
PA
D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D000077237:Arsenic Trioxide; D001152:Arsenicals / Q000494:pharmacology*; D048708:Cell Growth Processes / Q000187:drug effects; D045744:Cell Line, Tumor; D004305:Dose-Response Relationship, Drug; D016889:Endometrial Neoplasms / Q000188:drug therapy* / Q000201:enzymology / Q000235:genetics / Q000473:pathology; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D010087:Oxides / Q000494:pharmacology*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D019098:Telomerase / Q000037:antagonists & inhibitors* / Q000096:biosynthesis / Q000235:genetics
D000970:Antineoplastic Agents; D001152:Arsenicals; D010087:Oxides; D012333:RNA, Messenger; C509186:TERT protein, human; D019098:Telomerase; D000077237:Arsenic Trioxide