Arsenic trioxide exposure to ovarian carcinoma cells leads to decreased level of topoisomerase II and cytotoxicity.
The objective of this study was to investigate the effect of arsenic trioxide (As(2)O(3)) on topoisomerase II levels using western blotting method on MDAH 2774 ovarian carcinoma cell culture. Experimental designs were established to determine the cytotoxic effects of As(2)O(3) on MDAH 2774 cells and the IC50 (fatal dose for the 50% of cells) value. Cytotoxicity experiments were carried out using various concentrations of As(2)O(3). The 2,3-bis[2-methyloxy-4-nitro-5-sulfophenyl]-2H-tetrazolium-5-carboxanilide (XTT) and trypan blue dye-exclusion tests were used to evaluate cytotoxicity. Topoisomerase II expressions were investigated using western blotting method with various concentrations of As(2)O(3). Densitometric analysis of topoisomerase 2 bands was carried out using Quantity One 1-D analysis software (Bio-Rad USA, Life Science Research, Hercules, CA). IC50 value of As(2)O(3) was found to be 5 x 10(-6) M for MDAH 2774 cells. When the bands were evaluated, it was observed that there was a decrease in topoisomerase II levels in MDAH 2774 cells with increasing concentrations of As(2)O(3). It was also observed by the densitometric analysis that topoisomerase II expression ratios of MDAH 2774 cells were decreased by approximately 50% at this concentration. Topoisomerase II levels were significantly decreased with the increasing concentrations of As(2)O(3). Inhibition of topoisomerase II enzyme was one of the antiproliferative influence mechanisms of As(2)O(3).
Askar
N
N
Department of Obstetrics and Gynecology, Division of Medical Oncology, Ege University School of Medicine, Bornova, Izmir, Turkey.
Cirpan
T
T
Toprak
E
E
Karabulut
B
B
Selvi
N
N
Terek
M C
MC
Uslu
R
R
Sanli
U A
UA
Goker
E
E
D000970:Antineoplastic Agents / Q000633:toxicity*; D000077237:Arsenic Trioxide; D001152:Arsenicals; D015153:Blotting, Western; D049109:Cell Proliferation / Q000187:drug effects*; D004250:DNA Topoisomerases, Type II / Q000378:metabolism*; D015536:Down-Regulation; D005260:Female; D006131:Growth Inhibitors / Q000633:toxicity; D006801:Humans; D010051:Ovarian Neoplasms / Q000188:drug therapy* / Q000201:enzymology / Q000473:pathology; D010087:Oxides / Q000633:toxicity*; D014407:Tumor Cells, Cultured / Q000187:drug effects
D000970:Antineoplastic Agents; D001152:Arsenicals; D006131:Growth Inhibitors; D010087:Oxides; D004250:DNA Topoisomerases, Type II; D000077237:Arsenic Trioxide