Potential miRNAs involved in molecular pathways mediating the anticancer effects of short term starvation in breast cancer cells treated with doxorubicin

Background: In recent years, increasing evidences showed that several types of dietary approaches restricting food intake, including Short Term Starvation (STS), may exert a protective role against aging and other age-related pathologies as well as cancer. Interestingly, the dietary restriction showed significant anticancer effects able to prevent cancer onset, slow its progression and improve therapy response. Since recent studies showed that miRNAs may modulate sensibility/resistance to antiblastic therapy, the aim of our study was to investigate the STS-induced molecular changes in breast cancer cells treated with doxorubicin, focusing our attention on miRNA expression profile. Materials and methods: Vitality assays were used to assess the effects of STS on cell proliferation. Using a TaqMan Low Density Array A human microRNA microarray analysis, the expression profile of 377 miRNAs was analyzed in healthy and malignant breast cells, MCF10A and MDA-MB-231 respectively, treated for 24h with 1µM doxorubicin under STS conditions for 48h. In addition, the expression of mRNAs and miRNAs specifically induced by STS was analyzed in MCF-7, MDA-MB-231 and SkBr3 cells using Real-time PCR analyses. Results:In vitro cell vitality assays showed that STS, in association with doxorubicin treatment, significantly reduces breast cancer cell proliferation and viability, whereas it appears to protect healthy breast cells from chemotherapeutic treatment. Microarray analysis showed that a subset of miRNAs involved in molecular pathways related to drug sensitivity/resistance was found to be differentially expressed in breast cancer cells following the doxorubicin treatment and STS. Finally, expression analysis of hypothetical miRNA gene targets involved in therapy response have confirmed the coherence of our results. Conclusions: This work establishes, for the first time, an interesting link between anticancer effects of STS and miRNA expression changes in doxorubicin-treated breast cancer cells, suggesting the potential involvement of some miRNAs in molecular pathways mediating the effects of STS in breast cancer.