Resveratrol induces downregulation of DNA repair genes in MCF-7 human breast cancer cells.
To gain insights into the antitumor mechanisms of resveratrol (RES), we carried out a DNA microarray analysis in the breast cancer cell line MCF-7 to study the global gene expression profile induced by RES treatment. The mRNA expression level of 19 734 well-characterized human genes from MCF-7 cells was determined using Affymetrix microarrays under two different RES treatments: 150 μmol/l (IC(50)) and 250 μmol/l during 48 h. A total of 1211 genes were found to have altered mRNA expression levels of two-fold or more in the 150 μmol/l RES-treated group (518 upregulated and 693 downregulated genes). However, 2412 genes were found to have altered expression levels of two-fold or more in the 250 μmol/l RES-treated group (651 genes upregulated and 1761 downregulated). Under both conditions of RES treatment, several genes of mismatch repair, DNA replication, homologous recombination (HR), and cell cycle were strongly inhibited. Consistently, we found decreased protein levels of the MRN complex (MRE11-NBS1-RAD50), an important complex of the HR DNA repair pathway. The ability to inhibit the expression of DNA repair genes by RES could help to overcome drug resistance commonly shown by transformed cells and to provide a solid basis for carrying out clinical trials with RES, alone or in combination with other agents, to enhance treatment efficacy, reduce toxicity, and overcome chemoresistance. Remarkably, after RES treatment, we found a decrease in NBS1 and MRE11 protein levels, two major proteins involved in HR, which suggests that RES could be used to sensitize cancer cells to cell death in combination with anticancer drugs.
Department of Genetics and Molecular Biology, Center for Research and Advance Studies-National Polytechnic Institute, México DF, Mexico.
Ismael
I
Leon-Galicia
Jose
J
Diaz-Chavez
Enrique
E
Garcia-Villa
Laura
L
Uribe-Figueroa
Alfredo
A
Hidalgo-Miranda
Luis A
LA
Herrera
Elizabeth
E
Alvarez-Rios
Jaime
J
Garcia-Mena
Patricio
P
Gariglio
D020533:Angiogenesis Inhibitors / Q000494:pharmacology; D001943:Breast Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004260:DNA Repair / Q000187:drug effects* / Q000235:genetics*; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation / Q000187:drug effects* / Q000502:physiology; D005260:Female; D006801:Humans; D000077185:Resveratrol; D013267:Stilbenes / Q000494:pharmacology*
D020533:Angiogenesis Inhibitors; D013267:Stilbenes; D000077185:Resveratrol