Anders Øverbye

• Øverbye, Anders; Torgersen, Maria Lyngaas; Sønstevold, Tonje; Iversen, Tore Geir; Mørch, Ýrr Asbjørg & Skotland, Tore [Vis alle 7 forfattere av denne artikkelen] (2021). Cabazitaxel-loaded poly(alkyl cyanoacrylate) nanoparticles: Toxicity and changes in the proteome of breast, colon and prostate cancer cells. Nanotoxicology. ISSN 1743-5390. 15(7), s. 865–884. doi: 10.1080/17435390.2021.1924888. Fulltekst i vitenarkiv Vis sammendrag

  Nanoparticles composed of poly(alkyl cyanoacrylate) (PACA) have shown great promise due to their biodegradability and high drug loading capacity. Development of optimal PACA nanocarriers requires detailed analysis of the overall cellular impact exerted by PACA variants. We here perform a comprehensive comparison of cabazitaxel (CBZ)-loaded nanocarriers composed of three different PACA monomers, i.e. poly(n-butyl cyanoacrylate) (PBCA), poly(2-ethylbutyl cyanoacrylate) (PEBCA) and poly(octyl cyanoacrylate) (POCA). The cytotoxicity of drug-loaded and empty PACA nanoparticles were compared to that of free CBZ across a panel of nine cancer cell lines by assessing cellular metabolism, proliferation and protein synthesis. The analyses revealed that the cytotoxicity of all CBZ-loaded PACAs was similar to that of free CBZ for all cell lines tested, whereas the empty PACAs exerted much lower toxicity. To increase our understanding of the toxic effects of these treatments comprehensive MS-based proteomics were performed with HCT116, MDA-MB-231 and PC3 cells incubated with PACA-CBZ variants or free CBZ. Interestingly, PACA-CBZ specifically led to decreased levels of proteins involved in focal adhesion and stress fibers in all cell lines. Since we recently demonstrated that encapsulation of CBZ within PEBCA nanoparticles significantly improved the therapeutic effect of CBZ on a patient derived xenograft model in mice, we investigated the effects of this PACA variant more closely by immunoblotting. Interestingly, we detected several changes in the protein expression and degree of phosphorylation of SRC-pathway proteins that can be relevant for the therapeutic effects of these substances.

• Pathan, Mohashin; Keerthikumar, Shivakumar; Chisanga, David; Alessandro, Riccardo; Ang, Ching-Seng & Askenase, Philip [Vis alle 47 forfattere av denne artikkelen] (2017). A novel community driven software for functional enrichment analysis of extracellular vesicles data. Journal of Extracellular Vesicles. 6(1). doi: 10.1080/20013078.2017.1321455. Fulltekst i vitenarkiv
• Øverbye, Anders; Holsæter, Ann Mari; Fusser, Markus; Skalko-Basnet, Natasa; Iversen, Tore Geir & Torgersen, Maria Lyngaas [Vis alle 12 forfattere av denne artikkelen] (2017). Ceramide-containing liposomes with doxorubicin: time and cell-dependent effect of C6 and C12 ceramide. OncoTarget. 8(44), s. 76921–76934. doi: 10.18632/oncotarget.20217. Fulltekst i vitenarkiv Vis sammendrag

  Doxorubicin, a widely used chemotherapeutic drug, has several potential high- risk side effects including cardiomyopathy. Furthermore, cellular resistance to this drug develops with time. By using liposomes as carrier vesicles both the side effects and drug resistance might be avoided. In this study we have investigated the cytotoxic effect of doxorubicin encapsulated in liposomes with and without ceramides containing 6 or 12 carbon atoms in the N-amidated fatty acyl chains. The short-chain ceramide species were included in the liposomal compositions due to their pro-apoptotic properties, which might cause a synergistic anticancer effect. We demonstrate that the ceramide species enhance the liposomal doxorubicin toxicity in a cell-specific manner. The C6-ceramide effect is most pronounced in cervical cancer cells (HeLa) and colon cancer cells (HCT116), whereas the C12-ceramide effect is strongest in breast cancer cells (MDA-MB-231). Moreover, the study reveals the importance of investigating cell toxicity at several time points and in different cell-lines, to assess drug-and formulation-induced cytotoxic effects in vitro . Furthermore, our data show that the cytotoxicity obtained with the nanocarriers in vitro , does not necessarily reflect their ability to inhibit tumor growth in vivo . We speculate that the larger effect of Caelyx® than our liposomes in vivo is due to a greater in vivo stability of Caelyx®.

• Hessvik, Nina Pettersen; Øverbye, Anders; Brech, Andreas; Torgersen, Maria Lyngaas; Jakobsen, Ida Seim & Sandvig, Kirsten [Vis alle 7 forfattere av denne artikkelen] (2016). PIKfyve inhibition increases exosome release and induces secretory autophagy. Cellular and Molecular Life Sciences (CMLS). ISSN 1420-682X. 73(24), s. 4717–4737. doi: 10.1007/s00018-016-2309-8. Fulltekst i vitenarkiv
• Szalai, Paula; Hagen, Linda K Korsberg; Sætre, Frank; Luhr, Morten; Sponheim, Marianne & Øverbye, Anders [Vis alle 9 forfattere av denne artikkelen] (2015). Autophagic bulk sequestration of cytosolic cargo is independent of LC3, but requires GABARAPs. Experimental Cell Research. ISSN 0014-4827. 333(1), s. 21–38. doi: 10.1016/j.yexcr.2015.02.003. Fulltekst i vitenarkiv
• Øverbye, Anders; Skotland, Tore; Koehler, Christian; Thiede, Bernd; Seierstad, Therese & Berge, Viktor [Vis alle 8 forfattere av denne artikkelen] (2015). Identification of prostate cancer biomarkers in urinary exosomes. OncoTarget. 6(30), s. 30357–30376. doi: 10.18632/oncotarget.4851. Fulltekst i vitenarkiv
• Phuyal, Santosh; Skotland, Tore; Hessvik, Nina Pettersen; Simolin, Helena; Øverbye, Anders & Brech, Andreas [Vis alle 10 forfattere av denne artikkelen] (2015). The ether lipid precursor hexadecylglycerol stimulates the release and changes the composition of exosomes derived from PC-3 cells. Journal of Biological Chemistry. ISSN 0021-9258. 290, s. 4225–4237. doi: 10.1074/jbc.M114.593962. Fulltekst i vitenarkiv
• Øverbye, Anders; Sætre, Frank Ove; Hagen, Linda K Korsberg; Johansen, Harald Thidemann & Seglen, Per O. (2011). Autophagic activity measured in whole rat hepatocytes as the accumulation of a novel BHMT fragment (p10), generated in amphisomes by the asparaginyl proteinase, legumain. Autophagy. ISSN 1554-8627. 7(9), s. 1011–1027. doi: 10.4161/auto.7.9.16436. Fulltekst i vitenarkiv
• Øverbye, Anders & Seglen, Per O. (2009). Phosphorylated and non-phosphorylated forms of catechol O-methyltransferase in rat liver, brain and other tissues. Biochemical Journal. ISSN 0264-6021. 417, s. 535–545. doi: 10.1042/BJ20081284. Fulltekst i vitenarkiv
• Seglen, Per O.; Øverbye, Anders & Sætre, Frank (2009). Sequestration assays for mammalian autophagy. Methods in Enzymology. ISSN 0076-6879. 452, s. 63–83. doi: 10.1016/S0076-6879(08)03605-7. Fulltekst i vitenarkiv
• Øverbye, Anders; Fengsrud, Monica & Seglen, Per Ottar (2007). Proteomic analysis of membrane-associated proteins from rat liver autophagosomes. Autophagy. ISSN 1554-8627. 3(4), s. 300–322. Fulltekst i vitenarkiv Vis sammendrag

  Proteins associated with membranes from purified rat liver autophagosomes were separated by two-dimensional (2D) gel electrophoresis (zoom gels, pl 4-7 and 6-9), silver-stained and identified by MALDI-TOF mass spectrometry. Among >1,500 detectable protein spots, 58 (derived from 39 different known proteins) were at least twofold (and significantly) enriched in autophagosomal membranes relative to cytoplasmic membranes. All of these membrane-associated proteins were also present in the cytosol, many of them being truncated enzyme variants that would be expected to serve a binding rather than an enzymatic function. Eleven proteins were highly enriched (consistent with the theoretical maximum of 25x), corresponding to an exclusive membrane localization in the delimiting membrane of the autophagosome. Three of these were methyltransferases: betaine:homocysteine methyltransferase (five variants); catechol O-methyltransferase (one phosphorylated and one unphosphorylated variant) and methionine adenosyltransferase, perhaps indicating that methylation/demethylation of membrane components could play a role in autophagy. A fourth highly enriched autophagosomal protein, phosphatidylethanolamine binding protein, is particularly interesting considering that the autophagic marker protein, LC3/ Atg8, is linked to autophagosomal membranes through its covalent conjugation with phosphatidylethanolamine (as the form LC3-II). LC3-II was not detectable on silver-stained 2D-gels, but could be shown by immunoblotting to be highly enriched in autophagosomal membranes. Other highly enriched proteins were heat shock cognate protein Hsc70 (one short and one long variant), peroxiredoxin 2, peroxiredoxin 6 (two variants), fructose 1,6-bisphosphatase (one phosphorylated and one unphosphorylated variant), adenosine kinase, inorganic pyrophosphatase and selenium-binding protein 2. Hsc70, a chaperonin that plays an important role in the recognition and proteasomal degradation of aggregated proteins as well as in the lysosomal membrane uptake and degradation of certain cytosolic proteins (chaperone-mediated autophagy), could conceivably also serve a recognition function in the autophagic scavenging of denatured or aggregated proteins (aggrephagy). The moderately enriched (2-14x) autophagosomal membrane-associated proteins included a remarkably high proportion of drug-metabolizing enzymes, such as several glutathione S-transferases, sulfotransferases and aromatic hydrocarbon/steroid oxidoreductases. If the autophagic function of these proteins is to recognize protein-drug adducts, they may, along with the peroxiredoxins, chaperonins and methyl metabolic enzymes, make the phagophores (the sequestering precursors of the autophagosomal delimiting membrane) well equipped for the detection and scavenging of proteins denatured by oxidation, hypermethylation, drug adduction or other mechanisms.

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• Fusser, Markus; Øverbye, Anders; Pandya, Abhilash D.; Mørch, Ýrr Asbjørg; Borgos, Sven Even F. & Kildal, Wanja [Vis alle 16 forfattere av denne artikkelen] (2022). Corrigendum to “Cabazitaxel-loaded Poly(2-ethylbutyl cyanoacrylate) nanoparticles improve treatment efficacy in a patient derived breast cancer xenograft”, [Journal of Control Release, 293 (2019) 183–192, (Journal of Control Release, (2019) 293(183-192) (S0168365918306928), (10.1016/j.jconrel.2018.11.029)). Journal of Controlled Release. ISSN 0168-3659. 349, s. 1–1. doi: 10.1016/j.jconrel.2022.06.040. Fulltekst i vitenarkiv
• Torgersen, Maria Lyngaas; Szwed, Marzena; Sønstevold, Tonje; Øverbye, Anders; Engedal, Nikolai & Grallert, Beata [Vis alle 11 forfattere av denne artikkelen] (2018). Small variations in nanoparticle structure dictate differential cellular stress responses and mode of cell death. Fulltekst i vitenarkiv
• Øverbye, Anders; Holsæter, Ann Mari; Skalko-Basnet, Natasa; Tore-Geir, Iversen; Torgersen, Maria Lyngaas & Sønstevold, Tonje [Vis alle 8 forfattere av denne artikkelen] (2016). Biodegradable nanoparticles in cancer diagnosis and therapy (NANOCAN):Ceramide modulation of liposomal doxorubicin. Fulltekst i vitenarkiv

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