Anti-apoptotic action of zearalenone in MCF-7 cells.
Zearalenone (ZEA), a nonsteroidal estrogenic mycotoxin, is present in high concentrations in dairy products and cereals. Studies have indicated that ZEA could strongly provoke proliferation in estrogen-dependent breast cancer MCF-7 cells following estrogen ablation. The current study confirmed the previous studies that within the range of concentrations of 2-96nM, like endogenous estradiol, ZEA could stimulate proliferation in MCF-7 cells with inducing a profound increase in S phase and a modest increase in G(2)/M phase that was accompanied by a decrease in G(0)/G(1) phase. The Cell Death Detection ELISA was used to determine whether the robust cell viability retrieved by ZEA was a result of inhibited apoptosis. Data indicated that ZEA-mediated inhibition of apoptosis is significantly evident (P<0.05) and in a dose-dependent manner. Western blot and multiple RT-PCR analysis revealed that the anti-apoptotic bcl-2 was upregulated at both protein and mRNA levels, together with the downregulation of pro-apoptotic bax. In short, the results here showed that ZEA possessed comparative estrogenic activity and could promote the progression of MCF-7 cells through the cell cycle by a decrease in G(0)/G(1) phase and a significant increase in S phase. The pro-proliferative activity of ZEA was due to inhibition of apoptosis through regulation of bax/bcl-2 expression. Therefore, we conclude that contamination of ZEA in food might contribute to the increasing incidence rates of breast cancer.
Yu
Zengli
Z
Department of Nutrition and Food Hygiene, School of Public Health, Zhengzhou University, Zhengzhou, Henan Province 450052, China. yuzengli@263.net
Zhang
Lishi
L
Wu
Desheng
D
Liu
Fuyun
F
D017209:Apoptosis / Q000187:drug effects*; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004968:Estrogens, Non-Steroidal / Q000633:toxicity*; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000096:biosynthesis* / Q000235:genetics; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015025:Zearalenone / Q000633:toxicity*; D051028:bcl-2-Associated X Protein / Q000235:genetics / Q000378:metabolism*
D004968:Estrogens, Non-Steroidal; D019253:Proto-Oncogene Proteins c-bcl-2; D012333:RNA, Messenger; D051028:bcl-2-Associated X Protein; D015025:Zearalenone