Anti-leukemic properties of aplysinopsin derivative EE-84 alone and in combination with BH3 mimetic A-1210477

Published: 13 Dec 2019 | Version 1 | DOI: 10.17632/z2rkrgwbm9.1
Contributor(s):

Description of this data

Aplysinopsins are a class of marine indole alkaloids that exhibit a wide range of biological activities such as prevention of neoplastic growth on an array of different cancer cell lines. Although both the indole and N-benzyl moieties of aplysinopsins are known to possess anti-proliferative activity against cancer cells, their mechanism of action remains unclear. Through in vitro and in vivo proliferation and viability screening of newly synthesized aplysinopsin analogs on myelogenous leukemia cell lines and zebrafish toxicity tests as well as analysis of differential toxicity in non-cancerous RPMI 1788 cells, we identified EE-84 as a promising novel drug candidate against myeloid leukemia. This indole derivative demonstrated drug-likeness in agreement with Lipinski’s rule of five and was responsible for cell cycle dysregulation in K562 cells in line with its cytostatic effect. EE-84-treated K562 cells likewise underwent morphological changes suggesting mitochondrial dysfunction. Finally, we demonstrated the synergistic cytotoxic effect of EE-84 with a BH3 mimetic, the Mcl-1 inhibitor, A-1210477, against K562 cells, highlighting the inhibition of anti-apoptotic Bcl-2 proteins as a promising therapeutic approach against myeloid leukemia in combination with EE-84.

Experiment data files

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    • A
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      • Cell Titre Glo
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        Cite
    • C
      Cite
    • D
      Cite
      • Zebrafish Cardiotoxicity
        Cite
  • 6
    Cite
    • 1st
      Cite
      • 48h
        Cite
      • 72h
        Cite
    • 2nd
      Cite
      • 48h
        Cite
      • 72h
        Cite
    • 3rd
      Cite
      • 48H
        Cite
      • 72H
        Cite
  • 7
    Cite
    • A
      Cite
      • Diff Quik
        Cite
        • 24
          Cite
          • co
            Cite
            • 20x
              Cite
          • EE-84 50
            Cite
            • 20x
              Cite
        • 48
          Cite
          • 50
            Cite
            • 20x
              Cite
          • co
            Cite
            • 20x
              Cite
        • 72
          Cite
          • 50
            Cite
            • 20x
              Cite
          • co
            Cite
            • 20x
              Cite
        • 96
          Cite
    • B
      Cite
      • FSC vs. SSC
        Cite
        • 1st
          Cite
          • 24h
            Cite
          • 48H
            Cite
          • 72h
            Cite
            • RESOURCE.FRK
              Cite
          • 96h
            Cite
            • RESOURCE.FRK
              Cite
        • 2nd
          Cite
          • 24h
            Cite
          • 48h
            Cite
          • 72h
            Cite
            • RESOURCE.FRK
              Cite
          • 96h
            Cite
            • RESOURCE.FRK
              Cite
        • 3rd
          Cite
          • 24h
            Cite
          • 48H
            Cite
          • 72h
            Cite
          • 96h
            Cite
    • C
      Cite
      • Transmission Electron Microscopy
        Cite
        • EE-84, K562, TEM pictures
          Cite
          • 30 uM (24 h)
            Cite
            • 1
              Cite
            • 2
              Cite
            • 3
              Cite
            • 4 (REP)
              Cite
            • 5
              Cite
            • 6
              Cite
            • 7
              Cite
          • 30 uM (48 h)
            Cite
            • 1
              Cite
            • 10
              Cite
            • 11
              Cite
            • 12
              Cite
            • 13 (REP)
              Cite
            • 14
              Cite
            • 2
              Cite
            • 3
              Cite
            • 4
              Cite
            • 5
              Cite
            • 6
              Cite
            • 7
              Cite
            • 8
              Cite
            • 9
              Cite
          • 30 uM (72 h)
            Cite
            • 1
              Cite
            • 10
              Cite
            • 11
              Cite
            • 12 (REP)
              Cite
            • 2
              Cite
            • 3
              Cite
            • 4
              Cite
            • 5 (REP)
              Cite
            • 6 (REP)
              Cite
            • 7
              Cite
            • 8
              Cite
            • 9
              Cite
          • co (24h)
            Cite
            • 1
              Cite
            • 2
              Cite
            • 3 (REP)
              Cite
            • 4
              Cite
            • 5
              Cite
            • 6
              Cite
            • 7
              Cite
  • 8
    Cite
    • Western Blot
      Cite
      • EE84_K562_Mcl-1
        Cite
        • 1
          Cite
          • B actin
            Cite
            • ee84,k562,actin,1 2019.12.10_15.58.38-07_Ch
              Cite
            • ee84,k562,actin,1m 2019.12.10_16.09.22_Co
              Cite
          • Mcl-1
            Cite
            • ee84,k562,mcl1,1 2019.12.10_10.47.05-04_Ch
              Cite
            • ee84,k562,mcl1,1m 2019.12.10_10.51.30_Co
              Cite
        • 2
          Cite
          • B-actin
            Cite
            • ee84,k562,actin,2 2019.12.10_16.13.34-10_Ch
              Cite
            • ee84,k562,actin,2m 2019.12.10_16.20.55_Co
              Cite
          • Mcl-1
            Cite
            • ee84,k562,mcl1,2 2019.12.10_10.56.11-05_Ch
              Cite
            • ee84,k562,mcl1,2m 2019.12.10_10.58.24_Co
              Cite
        • 3 (REP)
          Cite
          • B actin
            Cite
            • ee84,k562,actin,3 2019.12.10_16.27.09-06_Ch
              Cite
            • ee84,k562,actin,3m 2019.12.10_16.35.52_Co
              Cite
          • Mcl-1
            Cite
            • ee84,k562,mcl1,3 2019.12.10_11.02.29-04_Ch
              Cite
            • ee84,k562,mcl1,3m 2019.12.10_11.04.10_Co
              Cite
  • 9
    Cite
    • A
      Cite
      • HoechstPI, combination, combination index
        Cite
        • 1st
          Cite
          • 10 + 30E
            Cite
          • 10+20E
            Cite
          • 10uM A
            Cite
          • 20uM EE-84
            Cite
          • 30uM EE-84
            Cite
          • 5+20E
            Cite
          • 5+30E
            Cite
          • 5uM A
            Cite
          • co
            Cite
        • 2nd
          Cite
          • 10A+20E
            Cite
          • 10A+30E
            Cite
          • 10uM A
            Cite
          • 5A+20E
            Cite
          • 5A+30E
            Cite
          • 5uM A
            Cite
          • co
            Cite
          • EE-84 20
            Cite
          • EE-84 30
            Cite
        • 3rd
          Cite
          • 10A
            Cite
          • 10A+20E
            Cite
          • 10A+30E
            Cite
          • 10A+40E
            Cite
          • 10A+50E
            Cite
          • 20E
            Cite
          • 30E
            Cite
          • 40E
            Cite
          • 50E
            Cite
          • co
            Cite
    • B
      Cite
      • combination index_compusyn
        Cite
    • C
      Cite
      • HOECHSTPI, combination+zvad_24h_K562
        Cite
        • 1st
          Cite
          • 10uM A-1210477
            Cite
          • 10uM A-1210477 + zvad
            Cite
          • 30uM EE-84
            Cite
          • 30uM EE-84 + zvad
            Cite
          • co
            Cite
          • co+zvad
            Cite
          • combination
            Cite
          • combination, zvad
            Cite
        • 2nd
          Cite
          • 10uM + ZVAD
            Cite
          • 10uM A-1210477
            Cite
          • 30uM EE-84
            Cite
          • 30uM EE-84 + zvad
            Cite
          • co
            Cite
          • co, zvad
            Cite
          • comb + zvad
            Cite
          • combination
            Cite
        • 3rd
          Cite
          • 10A+Zvad
            Cite
          • 10uM A-1210477
            Cite
          • 30E + Zvad
            Cite
          • 30uM EE-84
            Cite
          • co
            Cite
          • co+zvad
            Cite
          • comb+zvad
            Cite
          • combination
            Cite
  • Scheme 1
    Cite
  • Supplementary Data
    Cite
    • S1
      Cite
      • EE-115
        Cite
        • EE-115, K562
          Cite
        • EE-115, U937
          Cite
      • EE-118
        Cite
        • EE-118, K562
          Cite
        • EE-118, U937
          Cite
      • EE-31
        Cite
        • K562
          Cite
        • U937
          Cite
      • EE-80
        Cite
        • K562
          Cite
        • U937
          Cite
      • EE-84
        Cite
        • EE-84, K562
          Cite
        • EE-84, U937
          Cite
      • EE-92
        Cite
        • K562
          Cite
        • U937
          Cite
    • S2
      Cite
      • NMRs
        Cite
    • S3
      Cite
      • NMRs
        Cite
    • S4
      Cite
      • EE-115, RPMI1788
        Cite
      • EE-118, RPMI1788
        Cite
      • EE-84, RPMI1788
        Cite

Latest version

  • Version 1

    2019-12-13

    Published: 2019-12-13

    DOI: 10.17632/z2rkrgwbm9.1

    Cite this dataset

    Kim, Su A (2019), “Anti-leukemic properties of aplysinopsin derivative EE-84 alone and in combination with BH3 mimetic A-1210477”, Mendeley Data, v1 http://dx.doi.org/10.17632/z2rkrgwbm9.1

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