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@ARTICLE{Boulos:276989,
      author       = {J. C. Boulos and E. A. Omer and D. Rigano and C. Formisano
                      and M. Chatterjee and E. Leich and S. Klauck$^*$ and L.-T.
                      Shan and T. Efferth},
      title        = {{C}ynaropicrin disrupts tubulin and c-{M}yc-related
                      signaling and induces parthanatos-type cell death in
                      multiple myeloma.},
      journal      = {Acta pharmacologica Sinica},
      volume       = {44},
      number       = {11},
      issn         = {1671-4083},
      address      = {[Basingstoke]},
      publisher    = {Springer Nature},
      reportid     = {DKFZ-2023-01239},
      pages        = {2265-2281},
      year         = {2023},
      note         = {2023 Nov;44(11):2265-2281},
      abstract     = {The majority of blood malignancies is incurable and has
                      unforeseeable remitting-relapsing paths in response to
                      different treatments. Cynaropicrin, a natural sesquiterpene
                      lactone from the edible parts of the artichoke plant, has
                      gained increased attention as a chemotherapeutic agent. In
                      this study, we investigated the effects of cynaropicrin
                      against multiple myeloma (MM) cells in vitro and assessed
                      its in vivo effectiveness in a xenograft tumor zebrafish
                      model. We showed that cynaropicrin exerted potent
                      cytotoxicity against a panel of nine MM cell lines and two
                      leukemia cell lines with AMO1 being the most sensitive cell
                      line (IC50 = 1.8 ± 0.3 µM). Cynaropicrin (0.8, 1.9, 3.6
                      µM) dose-dependently reduced c-Myc expression and
                      transcriptional activity in AMO1 cells that was associated
                      with significant downregulation of STAT3, AKT, and ERK1/2.
                      Cell cycle analysis showed that cynaropicrin treatment
                      arrested AMO1 cells in the G2M phase along with an increase
                      in the sub-G0G1 phase after 24 h. With prolonged treatment
                      times, cells accumulated more in the sub-G0G1 phase,
                      implying cell death. Using confocal microscopy, we revealed
                      that cynaropicrin disrupted the microtubule network in U2OS
                      cells stably expressing α-tubulin-GFP. Furthermore, we
                      revealed that cynaropicrin promoted DNA damage in AMO1 cells
                      leading to PAR polymer production by PARP1 hyperactivation,
                      resulting in AIF translocation from the mitochondria to the
                      nucleus and subsequently to a novel form of cell death,
                      parthanatos. Finally, we demonstrated that cynaropicrin (5,
                      10 µM) significantly reduced tumor growth in a T-cell acute
                      lymphoblastic leukemia (T-ALL) xenograft zebrafish model.
                      Taken together, these results demonstrate that cynaropicrin
                      causes potent inhibition of hematopoietic tumor cells in
                      vitro and in vivo.},
      keywords     = {c-Myc (Other) / cynaropicrin (Other) / hematological
                      malignancies (Other) / microtubules (Other) / multiple
                      myeloma (Other) / network pharmacology (Other) / parthanatos
                      (Other) / xenograft tumor zebrafish model (Other)},
      cin          = {B063 / HD01},
      ddc          = {610},
      cid          = {I:(DE-He78)B063-20160331 / I:(DE-He78)HD01-20160331},
      pnm          = {312 - Funktionelle und strukturelle Genomforschung
                      (POF4-312)},
      pid          = {G:(DE-HGF)POF4-312},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:37344563},
      doi          = {10.1038/s41401-023-01117-3},
      url          = {https://inrepo02.dkfz.de/record/276989},
}