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@ARTICLE{Omer:304880,
      author       = {E. A. Omer and M. Zhou and W. P. Roos and L. J. Rashan and
                      H.-H. Fiebig and S. Klauck$^*$ and L. Shan and T. Efferth},
      title        = {{O}leandrin-mediated suppression of {MELK} induces
                      apoptosis, autophagy, and ferroptosis in human non-small
                      cell lung cancer cells.},
      journal      = {Phytomedicine},
      volume       = {147},
      issn         = {0944-7113},
      address      = {München [u.a.]},
      publisher    = {Elsevier},
      reportid     = {DKFZ-2025-01956},
      pages        = {157173},
      year         = {2025},
      abstract     = {Non-small-cell lung cancer NSCLC is the major diagnosed
                      type of lung cancers in the USA and Europe. It is generally
                      related to poor prognosis and low rates of survival.
                      Oleandrin is a cardiac glycoside occurring naturally in
                      Nerium oleander (Apocynaceae).To explore the potential
                      therapeutic value of oleandrin against different cancer
                      types with emphasis on NSCLC.The effect of oleandrin in
                      inhibiting the growth of different cancer cells was
                      measured. In addition, oleandrin activity in inhibiting cell
                      migration, suppression of MELK and inducing different modes
                      of cell deaths were investigated using in silico, in vitro,
                      and in vivo methods.Oleandrin showed activity at low
                      nanomolar level against 17 different types of cancer cells
                      including NSCLC. Our investigations in A549 cells indicated
                      that oleandrin is a MELK inhibitor, as it disrupted the
                      microtubule network and inhibited migration of A549 cells.
                      Moreover, it induced apoptosis, autophagy, and ferroptosis.
                      Furthermore, our in vivo data revealed that oleandrin had
                      significantly decreased tumor growth in a A549 xenograft
                      zebrafish model in a dose-dependent manner. In silico
                      analyses revealed that oleandrin bound to the ligand binding
                      pocket with higher binding affinity than the known inhibitor
                      MELK-8a. The binding was further confirmed in vitro using
                      microscale thermophoresis. An ADMET (absorption,
                      distribution, metabolism, excretion, toxicity) analysis,
                      together with our in vivo toxicity studies and the previous
                      clinical studies suggest that oleandrin has an acceptable
                      safety profile.Oleandrin could potentially have therapeutic
                      effects for NSCLC patients and possibly for other cancer
                      types.},
      keywords     = {Humans / Cardenolides: pharmacology / Carcinoma,
                      Non-Small-Cell Lung: drug therapy / Animals / Apoptosis:
                      drug effects / Zebrafish / Lung Neoplasms: drug therapy /
                      Autophagy: drug effects / Ferroptosis: drug effects / A549
                      Cells / Cell Movement: drug effects / Cell Line, Tumor /
                      Antineoplastic Agents, Phytogenic: pharmacology / Xenograft
                      Model Antitumor Assays / Nerium: chemistry / Cardiac
                      glycosides (Other) / In vivo (Other) / NSCLC (Other) /
                      Natural products (Other) / Nerium oleander (Other) /
                      Phytotherapy (Other) / Programmed cell death (Other) /
                      Cardenolides (NLM Chemicals) / oleandrin (NLM Chemicals) /
                      Antineoplastic Agents, Phytogenic (NLM Chemicals)},
      cin          = {B063},
      ddc          = {610},
      cid          = {I:(DE-He78)B063-20160331},
      pnm          = {312 - Funktionelle und strukturelle Genomforschung
                      (POF4-312)},
      pid          = {G:(DE-HGF)POF4-312},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:40916237},
      doi          = {10.1016/j.phymed.2025.157173},
      url          = {https://inrepo02.dkfz.de/record/304880},
}