Header

UZH-Logo

Maintenance Infos

Inhibition of DNA repair mechanisms and induction of apoptosis in triple negative breast cancer cells expressing the human herpesvirus 6 U94


Caccuri, Francesca; Sommariva, Michele; Marsico, Stefania; Giordano, Francesca; Zani, Alberto; Giacomini, Arianna; Fraefel, Cornel; Balsari, Andrea; Caruso, Arnaldo (2019). Inhibition of DNA repair mechanisms and induction of apoptosis in triple negative breast cancer cells expressing the human herpesvirus 6 U94. Cancers, 11(7):E1006.

Abstract

Triple-negative breast cancer (TNBC) accounts for 15-20% of all breast cancers. In spite of initial good response to chemotherapy, the prognosis of TNBC remains poor and no effective specific targeted therapy is readily available. Recently, we demonstrated the ability of U94, the latency gene of human herpes virus 6 (HHV-6), to interfere with proliferation and with crucial steps of the metastatic cascade by using MDA-MB 231 TNBC breast cancer cell line. U94 expression was also associated with a partial mesenchymal-to-epithelial transition (MET) of cells, which displayed a less aggressive phenotype. In this study, we show the ability of U94 to exert its anticancer activity on three different TNBC cell lines by inhibiting DNA damage repair genes, cell cycle and eventually leading to cell death following activation of the intrinsic apoptotic pathway. Interestingly, we found that U94 acted synergistically with DNA-damaging drugs. Overall, we provide evidence that U94 is able to combat tumor cells with different mechanisms, thus attesting for the great potential of this molecule as a multi-target drug in cancer therapy.

Abstract

Triple-negative breast cancer (TNBC) accounts for 15-20% of all breast cancers. In spite of initial good response to chemotherapy, the prognosis of TNBC remains poor and no effective specific targeted therapy is readily available. Recently, we demonstrated the ability of U94, the latency gene of human herpes virus 6 (HHV-6), to interfere with proliferation and with crucial steps of the metastatic cascade by using MDA-MB 231 TNBC breast cancer cell line. U94 expression was also associated with a partial mesenchymal-to-epithelial transition (MET) of cells, which displayed a less aggressive phenotype. In this study, we show the ability of U94 to exert its anticancer activity on three different TNBC cell lines by inhibiting DNA damage repair genes, cell cycle and eventually leading to cell death following activation of the intrinsic apoptotic pathway. Interestingly, we found that U94 acted synergistically with DNA-damaging drugs. Overall, we provide evidence that U94 is able to combat tumor cells with different mechanisms, thus attesting for the great potential of this molecule as a multi-target drug in cancer therapy.

Statistics

Citations

Dimensions.ai Metrics
4 citations in Web of Science®
3 citations in Scopus®
Google Scholar™

Altmetrics

Downloads

16 downloads since deposited on 07 Jan 2020
10 downloads since 12 months
Detailed statistics

Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:05 Vetsuisse Faculty > Institute of Virology
Dewey Decimal Classification:570 Life sciences; biology
Scopus Subject Areas:Health Sciences > Oncology
Life Sciences > Cancer Research
Uncontrolled Keywords:DNA repair; HHV-6 U94; HSV-1 amplicon vector; apoptosis; cell cycle; gene expression profile; triple negative breast cancer cells
Language:English
Date:18 July 2019
Deposited On:07 Jan 2020 15:39
Last Modified:22 Apr 2020 21:48
Publisher:MDPI Publishing
ISSN:2072-6694
OA Status:Gold
Free access at:PubMed ID. An embargo period may apply.
Publisher DOI:https://doi.org/10.3390/cancers11071006
PubMed ID:31323788

Download

Gold Open Access

Download PDF  'Inhibition of DNA repair mechanisms and induction of apoptosis in triple negative breast cancer cells expressing the human herpesvirus 6 U94'.
Preview
Content: Published Version
Language: English
Filetype: PDF
Size: 26MB
View at publisher
Licence: Creative Commons: Attribution 4.0 International (CC BY 4.0)