Biology subjects

Curtin, J.

Publications and source records attributed to Curtin, J..

2 recordsLinked to original sources

bioRxiv2020

Ursolic acid inhibits cell migration and promotes JNK-dependent lysosomal associated cell death in Glioblastoma multiforme cells

Ursolic acid (UA) is a bioactive compound which has demonstrated therapeutic efficacy in a variety of cancer cell lines. UA activates various signalling pathways in Glioblastoma multiforme (GBM), however, the relationship between cell death and migration has yet to be elucidated. UA induces a dose dependent cytotoxic response demonstrated by flow cytometry and biochemical cytotoxicity assays. Inhibitor and fluorescent probe studies demonstrated that UA induces a caspase independent, JNK dependent, mechanism of cell death. Migration studies established that UA inhibits GBM cell migration in a time dependent manner that is independent of the JNK signalling pathway. The cytotoxic insult induced by UA resulted in the formation of acidic vesicle organelles (AVOs), speculating activation of autophagy. However, inhibitor and spectrophotometric analysis demonstrated that autophagy was not responsible for the formation of the AVOs and confocal microscopy identified the AVOs as lysosomes. Further investigation using isosurface visualisation of confocal imaging determined co-localisation of lysosomes with the previously identified acidic vesicles, thus providing evidence that lysosomes are likely to be playing a role in UA induced cell death. Collectively, our data identifies that UA rapidly induces a lysosomal associated mechanism of cell death in addition to UA acting as an inhibitor of GBM cell migration. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=128 SRC="FIGDIR/small/987578v1_ufig1.gif" ALT="Figure 1"> View larger version (27K): org.highwire.dtl.DTLVardef@1b00447org.highwire.dtl.DTLVardef@e8e39eorg.highwire.dtl.DTLVardef@1b7d816org.highwire.dtl.DTLVardef@cb8d3b_HPS_FORMAT_FIGEXP M_FIG C_FIG

cancer biology↗

bioRxiv2020

Cold Atmospheric Plasma induces silver nanoparticle uptake, oxidative dissolution and enhanced cytotoxicity in Glioblastoma multiforme cells

Silver nanoparticles (AgNP) emerged as a promising reagent for cancer therapy with oxidative stress implicated in the toxicity. Meanwhile, studies reported cold atmospheric plasma (CAP) generation of reactive oxygen and nitrogen species has selectivity towards cancer cells. Gold nanoparticles display synergistic cytotoxicity when combined with CAP against cancer cells but there is a paucity of information using AgNP, prompting to investigate the combined effects of CAP using dielectric barrier discharge system (voltage of 75 kV, current is 62.5mA, duty cycle of 7.5kVA and input frequency of 50-60Hz) and 10nm PVA-coated AgNP using U373MG Glioblastoma Multiforme cells. Cytotoxicity in U373MG cells was >100-fold greater when treated with both CAP and PVA-AgNP compared with either therapy alone (IC50 of 4.30 g/mL with PVA-AgNP alone compared with 0.07 g/mL after 25s CAP and 0.01 g/mL 40s CAP). Combined cytotoxicity was ROS-dependent and was prevented using N-Acetyl Cysteine. A novel darkfield spectral imaging method investigated and quantified AgNP uptake in cells determining significantly enhanced uptake, aggregation and subcellular accumulation following CAP treatment, which was confirmed and quantified using atomic absorption spectroscopy. The results indicate that CAP decreases nanoparticle size, decreases surface charge distribution of AgNP and induces uptake, aggregation and enhanced cytotoxicity in vitro. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=65 SRC="FIGDIR/small/969758v1_ufig1.gif" ALT="Figure 1"> View larger version (16K): org.highwire.dtl.DTLVardef@6cacdcorg.highwire.dtl.DTLVardef@c8c9caorg.highwire.dtl.DTLVardef@381c5dorg.highwire.dtl.DTLVardef@1ce1ece_HPS_FORMAT_FIGEXP M_FIG C_FIG

cancer biology↗