title: A new anticancer toxin based on HER2/neu-specific DARPin and photoactive flavoprotein miniSOG.
abstract: Cytotoxic effects of a new targeted phototoxin DARPin-miniSOG and mechanism of its action were investigated in vitro. It was determined that DARPin-miniSOG causes light-induced death of HER2/neu-positive cancer cells (IC50 0.8 μM). Treatment of the cells with DARPin-miniSOG in the presence of ascorbic acid eliminated the light-induced cytotoxic action of the protein. This observation suggests the involvement of oxidative stress in the mechanism of the phototoxin action. DNA fragmentation analysis, caspase-3 activity assay and PI-staining of HER2/neu-positive cancer cells treated with DARPin-miniSOG indicated that phototoxin induces necrotic cell death under blue light illumination. Co-localization analysis showed that DARPin-miniSOG accumulates mostly in endosomes and lysosomes.
authors: Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Miklukho-Maklaya St, 16/10, Moscow 117997, Russia.
authors: G M
authors: GM
authors: Proshkina
authors: Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Miklukho-Maklaya St, 16/10, Moscow 117997, Russia.
authors: O N
authors: ON
authors: Shilova
authors: Prokhorov General Physics Institute, Russian Academy of Sciences, Vavilova St, 38, 119991 Moscow, Russia; National Research Nuclear University MEPhI (Moscow Engineering Physics Institute), Kashirskoe Highway, 31, Moscow 115409, Russia.
authors: A V
authors: AV
authors: Ryabova
authors: Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Miklukho-Maklaya St, 16/10, Moscow 117997, Russia.
authors: O A
authors: OA
authors: Stremovskiy
authors: Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Miklukho-Maklaya St, 16/10, Moscow 117997, Russia; Research Institute of Applied and Fundamental Medicine, Nizhny Novgorod State Medical Academy, Nizhny Novgorod, Russia. Electronic address: deyev@ibch.ru.
authors: S M
authors: SM
authors: Deyev
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D015153:Blotting, Western; D016466:CHO Cells; D016923:Cell Death / Q000187:drug effects; D003412:Cricetulus; D005420:Flavoproteins / Q000494:pharmacology; D006801:Humans; D018613:Microscopy, Confocal; D018384:Oxidative Stress; D010789:Phototherapy / Q000379:methods*; D056949:Phototropins / Q000494:pharmacology; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000494:pharmacology*; D020349:Surface Plasmon Resonance
chemical_list: D000970:Antineoplastic Agents; D005420:Flavoproteins; D056949:Phototropins; D018719:Erb-b2 Receptor Tyrosine Kinases; D011993:Recombinant Fusion Proteins; C508053:ERBB2 protein, human
keywords: Blue light illumination; DARPin; HER2/neu; miniSOG