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Jose Alexandre Marzagão Barbuto

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    P3.01 - Advanced NSCLC (Not CME Accredited Session) (ID 967)

    • Event: WCLC 2018
    • Type: Poster Viewing in the Exhibit Hall
    • Track:
    • Presentations: 1
    • Moderators:
    • Coordinates: 9/26/2018, 12:00 - 13:30, Exhibit Hall
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      P3.01-55 - SF2: A PCYT-2 Inhibitor Prototype is Capable of Inducing Citotoxicity in NSCLC (ID 14175)

      12:00 - 13:30  |  Author(s): Jose Alexandre Marzagão Barbuto

      • Abstract
      • Slides


      Lung cancer is one of the most common malignant tumors in the world and in most cases this disease has an unfavorable prognosis. Due to the relative failure of current therapeutic protocols, there is an urgent need for the development of new treatments. Then, new classes of drugs may be considered. The development of new drugs could benefit a large portion of the population affected by lung cancer. The enzyme CTP: phosphoethanolamine cytidylstransferase (Pcyt-2), which has phosphoethanolamine as the substrate, is a key regulator in the Kennedy pathway for the production of membrane phospholipids. Phosphoethanolamine is one of the most abundant phospholipids in eukaryotic cells and, therefore, the reduction of its production could directly affect cell division and apoptosis.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      In the present study it was evaluated the cytotoxic effects of a new prototype, named as SF2, in NSCLC. In order to evaluate the effect of SF2 on Pcyt-2; the radiolabeling assay of the intermediates of the Kennedy pathway was performed. The cytotoxic activity was investigated in A549 and NCI-H460 cell lines by the MTT colorimetric assay. Mitochondrial membrane depolarization and apoptosis analysis were performed by High Content Screening (HCS) using TMRE probe and double annexin V / PI labeling, respectively.

      4c3880bb027f159e801041b1021e88e8 Result

      SF2 was able to reduce the activity of Pcyt-2 enzyme (65% related to control group, p<0.01). This reduction also lead to the decrease of the CDP-ethanolamine (CDP-Etn) production (29%, p<0.001) and the transport of ethanolamine (Etn) (69% related to control, p<0.0001). SF2 presented IC50 values of 40 and 90 μM for A549 and NCI-H460 cell lines, respectively. In addition, SF2 was able to induce cell death by apoptosis in A549 (35% p<0.01) and in NCI-H460 (33%, p<0.03) and to reduce mitochondrial membrane potential of NCI-H460 cell line (27% related to control, p<0.05).

      8eea62084ca7e541d918e823422bd82e Conclusion

      Therefore, SF2 is a potential candidate of antitumor drug by the inhibition of Pcyt-2 enzyme in NSCLC models.


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