Selective cell cycle arrest in glioblastoma cell lines by quantum molecular resonance alone or in combination with temozolomide.

BACKGROUND: Glioblastoma is the most aggressive form of brain cancer, characterised by high proliferation rates and cell invasiveness. Despite advances in surgery and radio-chemotherapy, patients continue to have poor prognoses, with a survival rate of 14-15 months. Thus, new therapeutic strategies are needed. Non-ionising electromagnetic fields represent an emerging option given the potential advantages of safety, low toxicity and the possibility to be combined with other therapies. METHODS: Here, the anticancer activity of quantum molecular resonance (QMR) was investigated. For this purpose, three glioblastoma cell lines were tested, and the QMR effect was evaluated on cancer cell proliferation rate and aggressiveness. To clarify the QMR mechanism of action, the proteomic asset after stimulation was delineated. Mesenchymal stromal cells and astrocytes were used as healthy controls. RESULTS: QMR affected cancer cell proliferation, inducing a significant arrest of cell cycle progression and reducing cancer tumorigenicity. These parameters were not altered in healthy control cells. Proteomic analysis suggested that QMR acts not only on DNA replication but also on the machinery involved in the mitotic spindle assembly and chromosome segregation. Moreover, in a combined therapy assessment, QMR significantly enhanced temozolomide efficacy. CONCLUSIONS: QMR technology appears to be a promising tool for glioblastoma treatment.

In-vitro analysis of Quantum Molecular Resonance effects on human mesenchymal stromal cells.

Electromagnetic fields play an essential role in cellular functions interfering with cellular pathways and tissue physiology. In this context, Quantum Molecular Resonance (QMR) produces waves with a specific form at high-frequencies (4-64 MHz) and low intensity through electric fields. We evaluated the effects of QMR stimulation on bone marrow derived mesenchymal stromal cells (MSC). MSC were treated with QMR for 10 minutes for 4 consecutive days for 2 weeks at different nominal powers. Cell morphology, phenotype, multilineage differentiation, viability and proliferation were investigated. QMR effects were further investigated by cDNA microarray validated by real-time PCR. After 1 and 2 weeks of QMR treatment morphology, phenotype and multilineage differentiation were maintained and no alteration of cellular viability and proliferation were observed between treated MSC samples and controls. cDNA microarray analysis evidenced more transcriptional changes on cells treated at 40 nominal power than 80 ones. The main enrichment lists belonged to development processes, regulation of phosphorylation, regulation of cellular pathways including metabolism, kinase activity and cellular organization. Real-time PCR confirmed significant increased expression of MMP1, PLAT and ARHGAP22 genes while A2M gene showed decreased expression in treated cells compared to controls. Interestingly, differentially regulated MMP1, PLAT and A2M genes are involved in the extracellular matrix (ECM) remodelling through the fibrinolytic system that is also implicated in embryogenesis, wound healing and angiogenesis. In our model QMR-treated MSC maintained unaltered cell phenotype, viability, proliferation and the ability to differentiate into bone, cartilage and adipose tissue. Microarray analysis may suggest an involvement of QMR treatment in angiogenesis and in tissue regeneration probably through ECM remodelling.

Pulsed magnetic therapy increases osteogenic differentiation of mesenchymal stem cells only if they are pre-committed.

AIM: Pulsed electromagnetic field (PEMF) therapy has been documented to be an effective, non-invasive, safe treatment method for a variety of clinical conditions, especially in settings of recalcitrant healing. The underlying mechanisms on the different biological components of tissue regeneration are still to be elucidated. The aim of the present study was to characterize the effects of extremely low frequency (ELF)-PEMFs on commitment of mesenchymal stem cell (MSCs) culture system, through the determination of gene expression pattern and cellular morphology. MAIN METHODS: Human MSCs derived from adipose tissue (ADSCs) were cultured in presence of adipogenic, osteogenic, neural, or glial differentiative medium and basal medium, then exposed to ELF-PEMFs daily stimulation for 21days. Control cultures were performed without ELF-PEMFs stimulation for all cell populations. Effects on commitment were evaluated after 21days of cultures. KEY FINDINGS: The results suggested ELF-PEMFs does not influence ADSCs commitment and does not promote adipogenic, osteogenic, neural or glial differentiation. However, ELF-PEMFs treatment on ADSCs cultured in osteogenic differentiative medium markedly increased osteogenesis. SIGNIFICANCE: We concluded that PEMFs affect the osteogenic differentiation of ADSCs only if they are pre-commitment and that this therapy can be an appropriate candidate for treatment of conditions requiring an acceleration of repairing process.