title: Possible mechanisms of Leukoagglutinin induced apoptosis in human cells in vitro.
abstract: Leukoagglutinin is one of the phytohemagglutinin isolectins isolated from Phaseolus vulgaris. In our recent study, we showed that this lectin is able to influence the growth of human cancer cells in vitro. In addition, using the acridine orange and ethidium bromide staining, we found that leukoagglutinin can induce apoptosis. In order to understand the molecular mechanisms of induction of apoptosis, we performed computational modeling with subsequent experimental verification of theoretical data in vitro. We developed computational models of leukoagglutinin interaction with pro- (FasR and TNFR) and anti-apoptotic (IGF-1 and EGFR) receptors, and confirmed that leukoagglutinin may specifically interact with these receptors. Furthermore, we proved that leukoagglutinin can induce apoptosis in cancer (HEp-2) and non-cancer (4BL) cells, and observed that PHA-L is able to induce apoptosis through the up-regulation of Bax protein and activation of the effector caspase-3 and initiator caspase-8. However, these proteins have no effect on the Bcl-2 expression level.
authors.affiliation: Institute of Molecular Biology and Genetics National Academy of Science of Ukraine, 150 Zabolotnoho St., Kyiv, 03143, Ukraine.
authors.forename: Tetiana
authors.initials: T
authors.lastname: Kochubei
authors.affiliation: The Ukrainian Research Institute of Archival Affairs and Records Keeping (URIAARK), Department for Archival Affairs Technological Support, Sector for Archives Preservation Technologies Development, 24 Solomyanska St., Kyiv, 03110, Ukraine.
authors.forename: Volodymyr
authors.initials: V
authors.lastname: Kitam
authors.affiliation: Institute of Molecular Biology and Genetics National Academy of Science of Ukraine, 150 Zabolotnoho St., Kyiv, 03143, Ukraine.
authors.forename: Oksana
authors.initials: O
authors.lastname: Maksymchuk
authors.affiliation: Institute of Molecular Biology and Genetics National Academy of Science of Ukraine, 150 Zabolotnoho St., Kyiv, 03143, Ukraine.
authors.forename: Oksana
authors.initials: O
authors.lastname: Piven
authors.affiliation: Institute of Molecular Biology and Genetics National Academy of Science of Ukraine, 150 Zabolotnoho St., Kyiv, 03143, Ukraine.
authors.forename: Lyubov
authors.initials: L
authors.lastname: Lukash
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D053148:Caspase 3 / Q000378:metabolism; D053181:Caspase 8 / Q000378:metabolism; D045744:Cell Line, Tumor; D004789:Enzyme Activation / Q000187:drug effects; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D010835:Phytohemagglutinins / Q000737:chemistry / Q000494:pharmacology*; D011485:Protein Binding / Q000187:drug effects; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000378:metabolism; D015854:Up-Regulation / Q000187:drug effects; D051028:bcl-2-Associated X Protein / Q000235:genetics / Q000378:metabolism
chemical_list: D010835:Phytohemagglutinins; D012333:RNA, Messenger; D011956:Receptors, Cell Surface; D051028:bcl-2-Associated X Protein; C100156:leukoagglutinins, plants; D053148:Caspase 3; D053181:Caspase 8
keywords: cancer cells; docking; isolectin; lectin; phytohemagglutinin