TY - JOUR
T1 - Resveratrol inhibits cell cycle progression by targeting Aurora kinase A and Polo-like kinase 1 in breast cancer cells
AU - Medina-Aguilar, Rubiceli
AU - Marchat, Laurence A.
AU - Ocampo, Elena Arechaga
AU - Gariglio, Patricio
AU - Mena, Jaime García
AU - Sepúlveda, Nicolás Villegas
AU - Castillo, Macario Mart Ínez
AU - López-Camarill, César
PY - 2016/6
Y1 - 2016/6
N2 - The Aurora protein kinase (AURKA) and the Polo-like kinase-1 (PLK1) activate the cell cycle,and they are considered promising druggable targets in cancer therapy. However,resistance to chemotherapy and to specific small molecule inhibitors is common in cancer patients; thus alternative therapeutic approaches are needed to overcome clinical resistance. Here,we showed that the dietary compound resveratrol suppressed the cell cycle by targeting AURKA and PLK1 kinases. First,we identified genes modulated by resveratrol using a genome-wide analysis of gene expression in MDA-MB-231 breast cancer cells. Transcriptional profiling indicated that 375 genes were modulated at 24 h after resveratrol intervention,whereas 579 genes were regulated at 48 h. Of these,290 genes were deregulated in common at 24 and 48 h. Interestingly,a significant decrease in the expression of genes involved in the cell cycle,DNA repair,cytoskeleton organization,and angiogenesis was detected. In particular,AURKA and PLK1 kinases were downregulated by resveratrol at 24 h. In addition the BRCA1 gene,an AURKA/PLK1 inhibitor,was upregulated at 24 h of treatment. Moreover,two wellknown resveratrol effectors,cyclin D1 (CCND1) and cyclin B1 (CCNB1),were also repressed at both times. Congruently,we found that resveratrol impaired G1/S phase transition in both MDA-MB-231 and MCF-7 cells. By western blot assays,we confirmed that resveratrol suppressed AURKA,CCND1 and CCNB1 at 24 and 48 h. In summary,we showed for the first time that resveratrol regulates cell cycle progression by targeting AURKA and PLK1. Our findings highlight the potential use of resveratrol as an adjuvant therapy for breast cancer.
AB - The Aurora protein kinase (AURKA) and the Polo-like kinase-1 (PLK1) activate the cell cycle,and they are considered promising druggable targets in cancer therapy. However,resistance to chemotherapy and to specific small molecule inhibitors is common in cancer patients; thus alternative therapeutic approaches are needed to overcome clinical resistance. Here,we showed that the dietary compound resveratrol suppressed the cell cycle by targeting AURKA and PLK1 kinases. First,we identified genes modulated by resveratrol using a genome-wide analysis of gene expression in MDA-MB-231 breast cancer cells. Transcriptional profiling indicated that 375 genes were modulated at 24 h after resveratrol intervention,whereas 579 genes were regulated at 48 h. Of these,290 genes were deregulated in common at 24 and 48 h. Interestingly,a significant decrease in the expression of genes involved in the cell cycle,DNA repair,cytoskeleton organization,and angiogenesis was detected. In particular,AURKA and PLK1 kinases were downregulated by resveratrol at 24 h. In addition the BRCA1 gene,an AURKA/PLK1 inhibitor,was upregulated at 24 h of treatment. Moreover,two wellknown resveratrol effectors,cyclin D1 (CCND1) and cyclin B1 (CCNB1),were also repressed at both times. Congruently,we found that resveratrol impaired G1/S phase transition in both MDA-MB-231 and MCF-7 cells. By western blot assays,we confirmed that resveratrol suppressed AURKA,CCND1 and CCNB1 at 24 and 48 h. In summary,we showed for the first time that resveratrol regulates cell cycle progression by targeting AURKA and PLK1. Our findings highlight the potential use of resveratrol as an adjuvant therapy for breast cancer.
KW - AURKA
KW - BRCA1
KW - Breast cancer
KW - Cell cycle
KW - PLK1
KW - Resveratrol
KW - Transcriptome
UR - http://www.scopus.com/inward/record.url?scp=84964867587&partnerID=8YFLogxK
U2 - 10.3892/or.2016.4728
DO - 10.3892/or.2016.4728
M3 - Artículo
C2 - 27109433
SN - 1021-335X
VL - 35
SP - 3696
EP - 3704
JO - Oncology Reports
JF - Oncology Reports
IS - 6
ER -