BACKGROUND: Metabolic plasticity gives cancer cells the ability to shift between signaling pathways to facilitate their growth and survival. This study investigates the role of glucose deprivation in the presence and absence of beta-hydroxybutyrate (BHB) in growth, death, oxidative stress and the stemness features of lung cancer cells.
RESULTS: A549 cells were exposed to various glucose conditions, both with and without beta-hydroxybutyrate (BHB), to evaluate their effects on apoptosis, mitochondrial membrane potential, reactive oxygen species (ROS) levels using flow cytometry, and the expression of CD133, CD44, SOX-9, and β-Catenin through Quantitative PCR. The activity of superoxide dismutase, glutathione peroxidase, and malondialdehyde was assessed using colorimetric assays. Treatment with therapeutic doses of BHB triggered apoptosis in A549 cells, particularly in cells adapted to glucose deprivation. The elevated ROS levels, combined with reduced levels of SOD and GPx, indicate that oxidative stress contributes to the cell arrest induced by BHB. Notably, BHB treatment under glucose-restricted conditions notably decreased CD133 expression, suggesting a potential inhibition of cell survival through the downregulation of CD133 levels. Additionally, the simultaneous decrease in mitochondrial membrane potential and increase in ROS levels indicate the potential for creating oxidative stress conditions to impede tumor cell growth in such environmental settings.
CONCLUSIONS: The induced cell death, oxidative stress and mitochondria impairment beside attenuated levels of cancer stem cell markers following BHB administration emphasize on the distinctive role of metabolic plasticity of cancer cells and propose possible therapeutic approaches to control cancer cell growth through metabolic fuels.

A growing body of evidence suggests that anesthetics impact the outcome of patients with cancer after surgical intervention. However, the optimal dose and underlying mechanisms of co-administered anesthetics in lung tumor therapy have been poorly studied. Here, we aimed to investigate the role of combined anesthetics propofol, sufentanil, and rocuronium in treating lung cancer using an orthogonal experimental design and to explore the optimal combination of anesthetics. First, we evaluated the effects of the three anesthetics on the proliferation and invasion of A-549 cells using Cell Counting Kit 8 and Transwell migration and invasion assays. Subsequently, we applied the orthogonal experimental design (OED) method to screen the appropriate concentrations of the combined anesthetics with the most effective antitumor activity. We found that all three agents inhibited the proliferation of A-549 cells in a dose- and time-dependent manner when applied individually or in combination, with the highest differences in the magnitude of inhibition occurring 24 h after combined drug exposure. The optimal combination of the three anesthetics that achieved the strongest reduction in cell viability was 1.4 µmol/L propofol, 2 nmol/L sufentanil, and 7.83 µmol/L rocuronium. This optimal 3-drug combination produced a more beneficial result at 24 h than either single drug. Our results provide a theoretical basis for improving the efficacy of lung tumor treatment and optimizing anesthetic strategies.

The combination of magnetic hyperthermia with chemotherapy is considered a promising strategy in cancer therapy due to the synergy between the high temperatures and the chemotherapeutic effects, which can be further developed for targeted and remote-controlled drug release. In this paper we report a simple, rapid, and reproducible method for the preparation of thermosensitive magnetoliposomes (TsMLs) loaded with doxorubicin (DOX), consisting of a lipidic gel formation from a previously obtained water-in-oil microemulsion with fine aqueous droplets containing magnetic nanoparticles (MNPs) dispersed in an organic solution of thermosensitive lipids (transition temperature of ~43 °C), followed by the gel hydration with an aqueous solution of DOX. The obtained thermosensitive magnetoliposomes (TsMLs) were around 300 nm in diameter and exhibited 40% DOX incorporation efficiency. The most suitable MNPs to incorporate into the liposomal aqueous lumen were Zn ferrites, with a very low coercive field at 300 K (7 kA/m) close to the superparamagnetic regime, exhibiting a maximum absorption rate (SAR) of 1130 W/gFe when dispersed in water and 635 W/gFe when confined inside TsMLs. No toxicity of Zn ferrite MNPs or of TsMLs was noticed against the A459 cancer cell line after 48 h incubation over the tested concentration range. The passive release of DOX from the TsMLs after 48h incubation induced a toxicity starting with a dosage level of 62.5 ug/cm2. Below this threshold, the subsequent exposure to an alternating magnetic field (20-30 kA/m, 355 kHz) for 30 min drastically reduced the viability of the A459 cells due to the release of incorporated DOX. Our results strongly suggest that TsMLs represent a viable strategy for anticancer therapies using the magnetic field-controlled release of DOX.

The influenza virus NS1 protein interacts with a wide range of proteins to suppress the host cell immune response and facilitate virus replication. The amino acid sequence of the 2009 pandemic virus NS1 protein differed from sequences of earlier related viruses. The functional impact of these differences has not been fully defined. Therefore, we made mutations to the NS1 protein based on these sequence differences, and assessed the impact of these changes on host cell interferon (IFN) responses. We found that viruses with mutations at position 171 replicated efficiently but did not induce expression of interferon genes as effectively as wild-type viruses in A459 lung epithelial cells. The decreased ability of these NS1 mutant viruses to induce IFN gene and protein expression correlated with decreased activation of STAT1 and lower levels of IFN-stimulated gene (ISG) expression. These findings demonstrate that mutations at position 171 in the NS1 protein result in decreased expression of IFN and ISGs by A549 cells. Consequently, these viruses may be more virulent than the parental strains that do not contain mutations at position 171 in the NS1 protein.