Resveratrol decreases Rad51 expression and sensitizes cisplatin-resistant MCF-7 breast cancer cells
Por:
Leon-Galicia I., Diaz-Chavez J., Albino-Sanchez M.E., Garcia-Villa E., Bermudez-Cruz R., Garcia-Mena J., Herrera L.A., GARCíA-CARRANCá A., Gariglio P.
Publicada:
1 jun 2018
Resumen:
Resveratrol (RES), a polyphenol compound with anti-proliferative
properties, has been previously evaluated for its beneficial effects
against a variety of tumour cells. The current study elucidated the
means by which RES enhances the anti-proliferative effects of cisplatin
(CIS) on MCF-7 cells, focusing on the inhibitory effects on DNA repair
of double-strand breaks (DSBs). Chemoresistant MCF-7 cells (MCF-7R) were
generated by continuous exposure to low concentrations of CIS (10 mu M
CIS-IC40) during 5 passages, with the IC50 value increasing similar to
3-fold. Using an MTT assay, we estimated the changes in IC50 for CIS in
MCF-7, T47-D, MDA-MB-231 and MCF-7R cells in the presence of RES. The
relative transcript level of Nbs-1, Mre-11 and Rad-50 genes was assessed
using RT-qPCR analysis. Rad51 and H2AX [pSer139] protein expression
was determined by western blot analysis. RES at 50 and 100 mu M
significantly enhanced the anti-proliferative effects of CIS in both
MCF-7 and MCF-7R cells, decreasing the IC50 values for CIS to one-tenth
and one-sixth, respectively. A total of 100 mu M RES decreased the
relative transcript levels of homologous recombination (HR) initiation
complex components and the Rad51 protein level in MCF-7 and MCF-7R
cells. After 48 h of CIS DNA damage, the levels of Rad51 protein
increased, but this effect was inhibited by 100 mu M RES. RES also
maintained serine 139 phosphorylation of histone H2AX, suggesting that
RES prevents the repair of DSBs. It was observed that RES exerts an
antagonistic effect over CIS on the activation of Rad51 and sustained
phosphorylation of H2AX. The results suggest that RES in combination
with DNA damage-based therapy has potential as a strategy to overcome
resistance and provide much safer and more effective treatment for
breast cancer.
Filiaciones:
Leon-Galicia I.:
Biomedical Unit for Cancer Research, virus and Cancer Laboratory, Department of Basic Research, Instituto de Investigaciones Biomédicas, UNAM, Instituto Nacional de Cancerologia (INCan), Mexico
Univ Nacl Autonoma Mexico, Inst Nacl Cancerol INCan, Biomed Unit Canc Res,Inst Invest Biomed, Virus & Canc Lab,Dept Basic Res, Mexico City 14080, DF, Mexico
Diaz-Chavez J.:
Biomedical Unit for Cancer Research, Carcinogenesis Laboratory, Department of Basic Research, Instituto de Investigaciones Biomédicas, UNAM/Instituto Nacional de Cancerologia (INCan), Mexico City, Mexico
Univ Nacl Autonoma Mexico, Inst Nacl Cancerol INCan, Biomed Unit Canc Res,Inst Invest Biomed, Carcinogenesis Lab,Dept Basic Res, Mexico City 14080, DF, Mexico
Biomedical Unit for Cancer Research, Carcinogenesis Laboratory, Department of Basic Research, Instituto de Investigaciones Biomédicas, UNAM/Instituto Nacional de Cancerologia (INCan), Mexico City, 14080, Mexico
Albino-Sanchez M.E.:
Department of Genetics and Molecular Biology, Center of Research and Advanced Studies (CINVESTAV-IPN), Mexico City, Mexico
IPN, CINVESTAV, Dept Genet & Mol Biol, Ctr Res & Adv Studies, Av IPN 2508, Mexico City 07360, DF, Mexico
Department of Genetics and Molecular Biology, Center of Research and Advanced Studies (Cinvestav-IPN), Mexico City, 07360, Mexico
Garcia-Villa E.:
Department of Genetics and Molecular Biology, Center of Research and Advanced Studies (CINVESTAV-IPN), Mexico City, Mexico
IPN, CINVESTAV, Dept Genet & Mol Biol, Ctr Res & Adv Studies, Av IPN 2508, Mexico City 07360, DF, Mexico
Department of Genetics and Molecular Biology, Center of Research and Advanced Studies (Cinvestav-IPN), Mexico City, 07360, Mexico
Bermudez-Cruz R.:
Department of Genetics and Molecular Biology, Center of Research and Advanced Studies (CINVESTAV-IPN), Mexico City, Mexico
IPN, CINVESTAV, Dept Genet & Mol Biol, Ctr Res & Adv Studies, Av IPN 2508, Mexico City 07360, DF, Mexico
Department of Genetics and Molecular Biology, Center of Research and Advanced Studies (Cinvestav-IPN), Mexico City, 07360, Mexico
Garcia-Mena J.:
Department of Genetics and Molecular Biology, Center of Research and Advanced Studies (CINVESTAV-IPN), Mexico City, Mexico
IPN, CINVESTAV, Dept Genet & Mol Biol, Ctr Res & Adv Studies, Av IPN 2508, Mexico City 07360, DF, Mexico
Department of Genetics and Molecular Biology, Center of Research and Advanced Studies (Cinvestav-IPN), Mexico City, 07360, Mexico
Herrera L.A.:
Biomedical Unit for Cancer Research, Carcinogenesis Laboratory, Department of Basic Research, Instituto de Investigaciones Biomédicas, UNAM/Instituto Nacional de Cancerologia (INCan), Mexico City, Mexico
Univ Nacl Autonoma Mexico, Inst Nacl Cancerol INCan, Biomed Unit Canc Res,Inst Invest Biomed, Carcinogenesis Lab,Dept Basic Res, Mexico City 14080, DF, Mexico
Biomedical Unit for Cancer Research, Carcinogenesis Laboratory, Department of Basic Research, Instituto de Investigaciones Biomédicas, UNAM/Instituto Nacional de Cancerologia (INCan), Mexico City, 14080, Mexico
GARCíA-CARRANCá A.:
Biomedical Unit for Cancer Research, virus and Cancer Laboratory, Department of Basic Research, Instituto de Investigaciones Biomédicas, UNAM, Instituto Nacional de Cancerologia (INCan), Mexico
Univ Nacl Autonoma Mexico, Inst Nacl Cancerol INCan, Biomed Unit Canc Res,Inst Invest Biomed, Virus & Canc Lab,Dept Basic Res, Mexico City 14080, DF, Mexico
Gariglio P.:
Department of Genetics and Molecular Biology, Center of Research and Advanced Studies (CINVESTAV-IPN), Mexico City, Mexico
Department of Genetics and Molecular Biology, Center of Research and Advanced Studies (Cinvestav-IPN), Av. IPN 2508, Col. San Pedro zacatenco, Mexico City, Mexico
IPN, CINVESTAV, Dept Genet & Mol Biol, Ctr Res & Adv Studies, Av IPN 2508, Mexico City 07360, DF, Mexico
Department of Genetics and Molecular Biology, Center of Research and Advanced Studies (Cinvestav-IPN), Mexico City, 07360, Mexico
Department of Genetics and Molecular Biology, Center of Research and Advanced Studies (Cinvestav-IPN), Av. IPN 2508, Col. San Pedro zacatenco, Mexico City, 07360, Mexico
|