English (United Kingdom)

https://curated-unify.zendy.io/wp-json/zendy-region/v1/featured_content/oa?rat=en

https://curated-unify.zendy.io/wp-json/zendy-region/v1/highlighted_journal/

Global: Zendy Plus annual

Presents the access of premium content as premium feature

Premium Content

Presents the keyphrase highlighting as premium feature

Keyphrase Highlighting

Presents the summarisation as premium feature

Summarisation

Insights

Presents the pdf analysis as premium feature

PDF Analysis

Presents the zaia usage as premium feature

ZAIA

Global: Zendy Plus monthly

Global: Zendy Tools annual

Global: Zendy Tools monthly

Global: Zendy Free Plan

Recently, we have shown that the antiangiogenic pigment epithelium-derivedfactor (PEDF) can bind the catalytic β-subunit of F1-ATP synthase and inhibitendothelial cell surface ATP synthase activity. This factor can additionally restricttumor growth, invasion and metastasis, and can directly induce death on severaltumor cell types. Active cell surface ATP synthase is also present in certaintumor cells and its ATP product is considered a stimulus for tumor growth. Thepresent study aimed to elucidate the biological implications of the interactionsbetween the extracellular PEDF and tumor cell surface ATP synthase. Incubationof T24 human urinary bladder carcinoma cells in media containing human recombinantPEDF protein for 48-96 h dramatically decreased cell viability in a concentration-dependentfashion as monitored by real-time cell impedance with a microelectronic system,microscopic imaging and biomarkers of live cells. Intact tumor cells exhibitedcell surface ATP synthesis activity, which was inhibited by piceatannol, a specificinhibitor of F1/F0-ATP synthase. Immunoblotting revealed that the β subunit ofF1-ATP synthase was present in plasma membrane fractions of these cells. Interestingly,pre-incubation of tumor cells with PEDF inhibited the activity of cell surfaceATP synthase in a concentration-dependent fashion. The PEDF-derived peptide 34-merdecreased tumor cell viability and inhibited extracellular ATP synthesis to thesame extent as full-length PEDF. Moreover, ATP additions attenuated both the PEDF-mediateddecrease in tumor cell viability and the inhibition of endothelial cell tube formation.The results lead to conclude that PEDF is a novel inhibitor of tumor cell surfaceATP synthase activity that exhibits a cytotoxic effect on tumor cells, and thatthe structural determinants for these properties are within the peptide region34-mer of the PEDF polypeptide. The data strongly suggest a role for the interactionbetween the 34-mer region of PEDF and tumor cell-surface ATP synthase in promotingtumor cell death.

Inhibition of tumor cell surface ATP synthesis by pigment epithelium-derived factor: Implications for antitumor activity