期刊
MOLECULES
卷 27, 期 4, 页码 -出版社
MDPI
DOI: 10.3390/molecules27041299
关键词
peptide nucleic acids; sulforaphane; glioblastoma; microRNAs; miR-15b-5p; miRNA targeting; combined therapy
资金
- Associazione Italiana per la Ricerca sul Cancro (AIRC) [13575]
- Interuniversity Consortium for the Biotechnology, Italy (C.I.B)
- FIRC-AIRC Michele e Carlo Ardizzone fellowship [25528]
- FAR (University Fund for Scientific Research, FAR-AF-Unife-2020)
- FIR (University Fund for Incentive of Research, FIR-AF-Unife-2020)
Glioblastoma multiforme (GBM) is a highly lethal tumor with no curative treatment available. This study investigated the potential of a combined therapy using sulforaphane (SFN) and a peptide nucleic acid (PNA) to target miR-15b-5p in GBM cells. The results showed that SFN and PNA-a15b synergistically induced apoptosis in GBM cells, suggesting the feasibility of using combined treatments based on PNAs and nutraceuticals to stimulate apoptosis in GBM.
Glioblastoma multiforme (GBM) is a lethal malignant tumor accounting for 42% of the tumors of the central nervous system, the median survival being 15 months. At present, no curative treatment is available for GBM and new drugs and therapeutic protocols are urgently needed. In this context, combined therapy appears to be a very interesting approach. The isothiocyanate sulforaphane (SFN) has been previously shown to induce apoptosis and inhibit the growth and invasion of GBM cells. On the other hand, the microRNA miR-15b is involved in invasiveness and proliferation in GBM and its inhibition is associated with the induction of apoptosis. On the basis of these observations, the objective of the present study was to determine whether a combined treatment using SFN and a peptide nucleic acid interfering with miR-15b-5p (PNA-a15b) might be proposed for increasing the pro-apoptotic effects of the single agents. To verify this hypothesis, we have treated GMB U251 cells with SFN alone, PNA-a15b alone or their combination. The cell viability, apoptosis and combination index were, respectively, analyzed by calcein staining, annexin-V and caspase-3/7 assays, and RT-qPCR for genes involved in apoptosis. The efficacy of the PNA-a15b determined the miR-15b-5p content analyzed by RT-qPCR. The results obtained indicate that SFN and PNA-a15b synergistically act in inducing the apoptosis of U251 cells. Therefore, the PNA-a15b might be proposed in a combo-therapy associated with SFN. Overall, this study suggests the feasibility of using combined treatments based on PNAs targeting miRNA involved in GBM and nutraceuticals able to stimulate apoptosis.
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