Inhibition of telomerase activity and cell proliferation by a reverse transcriptase inhibitor in gynaecological cancer cell lines.
Telomerase is a ribonucleoprotein which has a RNA template to bind and extend telomere ends, so prolonging the life of tumour cells. The aim of this study was to determine whether transcriptase function of telomerase could be inhibited by the reverse transcriptase inhibitors (RTI); azydothymidine (AZT), dideoxyinosine (ddI) and AZT-5' triphosphate (AZT-TP). We examined their effects on the proliferation of cancer cells and the antitumour effects of cisplatin in vitro. The three agents did not cause major changes in telomerase activity or telomere length in MCAS cells. However, in HEC-1 cells changes in telomerase activity and telomere length were observed that were dependent on the RTI concentration and duration of exposure. ddI and AZT-TP reduced telomerase activity and shortened the length of the telomere. In the presence of RTI, the antitumour effects of cisplatin were enhanced. This was particularly evident in HEC-1 cells where there was a marked reduction in cell proliferation, appearance of morphological changes and senescent-like cells in the presence of ddI or AZT-TP. In MCAS cells, TP53 expression was increased by ddI and AZT-TP, while p21 expression was unchanged. In HEC-1 cells the expression of both TP53 and P21 was increased by ddI. Continuous administration of RTI enhanced the cell growth inhibition of cisplatin. RTI also inhibited the proliferation of some cells.
Murakami
J
J
Department of Obstetrics and Gynecology, Hiroshima University School of Medicine, Japan.
Nagai
N
N
Shigemasa
K
K
Ohama
K
K
D015139:Blotting, Southern; D002455:Cell Division; D003536:Cystadenocarcinoma / Q000201:enzymology* / Q000473:pathology; D016049:Didanosine / Q000494:pharmacology; D054306:Dideoxynucleotides; D016889:Endometrial Neoplasms / Q000201:enzymology / Q000473:pathology; D005260:Female; D054303:HIV Reverse Transcriptase / Q000037:antagonists & inhibitors; D006801:Humans; D018894:Reverse Transcriptase Inhibitors / Q000494:pharmacology*; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D019098:Telomerase / Q000037:antagonists & inhibitors*; D013942:Thymine Nucleotides / Q000494:pharmacology; D014407:Tumor Cells, Cultured; D014594:Uterine Neoplasms / Q000201:enzymology* / Q000473:pathology; D015215:Zidovudine / Q000031:analogs & derivatives / Q000494:pharmacology
D054306:Dideoxynucleotides; D018894:Reverse Transcriptase Inhibitors; D013942:Thymine Nucleotides; D015215:Zidovudine; C052873:zidovudine triphosphate; D054303:HIV Reverse Transcriptase; D019098:Telomerase; D016049:Didanosine