title: Nordihydroguaiaretic acid restores expression of silenced E-cadherin gene in human breast cancer cell lines and xenografts.
abstract: In our study we use nordihydroguaiaretic acid (NDGA), the naturally occurring lignan, to investigate whether it plays a role in the prevention and treatment of cancer by epigenetic modifications. The growth inhibitory effect of NDGA on human breast cancer cell lines was determined using the MTT assay (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide assay). It substantially inhibited the growth of human breast cancer cell lines SKBR3 and MDA-MB-435 with an estimated IC50 of 31.09+/-1.6 and 38.8+/-2.1 micromol/l respectively, after 4 days incubation with different NDGA concentrations. The in-vivo anticancer activity of NDGA was evaluated by calculating the tumor growth inhibition value. NDGA substantially inhibited the growth of human breast carcinoma cells in both animal and cell-based models. We also found that a single treatment with NDGA reactivates methylation-silenced E-cadherin gene in vitro and in vivo, suggesting an intriguing concept that lignans may act as natural effective epigenetic modifiers in the prevention and treatment of cancer.
authors.affiliation: Reproductive and Genetic Center of National Research Institute for Family Planning, Peking University, Beijing, China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Cui
authors.forename: Cailing
authors.initials: C
authors.lastname: Lu
authors.forename: Aijun
authors.initials: A
authors.lastname: Kang
authors.forename: Liyong
authors.initials: L
authors.lastname: Liu
authors.forename: Sainan
authors.initials: S
authors.lastname: Tan
authors.forename: Daguang
authors.initials: D
authors.lastname: Sun
authors.forename: Jianguo
authors.initials: J
authors.lastname: Hu
authors.forename: Xu
authors.initials: X
authors.lastname: Ma
mesh_terms: D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D001943:Breast Neoplasms; D015820:Cadherins / Q000096:biosynthesis* / Q000235:genetics; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D019175:DNA Methylation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D044127:Epigenesis, Genetic; D005260:Female; D020868:Gene Silencing; D006801:Humans; D009637:Masoprocol / Q000494:pharmacology*; D051379:Mice; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D014183:Transplantation, Heterologous
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D015820:Cadherins; D009637:Masoprocol