Marine bisindole alkaloid: A potential apoptotic inducer in human cancer cells

  • Sara Salucci | sara.salucci@uniurb.it University of Urbino, Department of Biomolecular Sciences, Italy.
  • Sabrina Burattini University of Urbino, Department of Biomolecular Sciences, Italy.
  • Francesca Buontempo University of Bologna, Department of Biomedical and Neuromotor Sciences, Italy.
  • Ester Orsini University of Bologna, Department of Biomedical and Neuromotor Sciences, Italy.
  • Lucia Furiassi University of Urbino, Department of Biomolecular Sciences, Italy.
  • Michele Mari University of Urbino, Department of Biomolecular Sciences, Italy.
  • Simone Lucarini University of Urbino, Department of Biomolecular Sciences, Italy.
  • Alberto M. Martelli University of Bologna, Department of Biomedical and Neuromotor Sciences, Italy.
  • Elisabetta Falcieri University of Urbino, Department of Biomolecular Sciences, Italy.

Abstract

Marine organisms such as corals, sponges and tunicates produce active molecules which could represent a valid starting point for new drug development processes. Among the various structural classes, the attention has been focused on 2,2-bis(6-bromo-3-indolyl) ethylamine, a marine alkaloid which showed a good anticancer activity against several tumor cell lines. Here, for the first time, the mechanisms of action of 2,2-bis(6-bromo-3-indolyl) ethylamine have been evaluated in a U937 tumor cell model. Morpho-functional and molecular analyses, highlighting its preferred signaling pathway, demonstrated that apoptosis is the major death response induced by this marine compund. Chromatin condensation, micronuclei formation, blebbing and in situ DNA fragmentation, occurring through caspase activation (extrinsic and intrinsic pathways), were observed. In particular, the bisindole alkaloid induces a mitochondrial involvement in apoptosis machinery activation with Blc-2/Bcl-x down-regulation and Bax up-regulation. These findings demonstrated that 2,2-bis(6-bromo-3-indolyl) ethylamine alkaloid-induced apoptosis is regulated by the Bcl-2 protein family upstream of caspase activation.

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Published
2018-04-10
Section
Original Papers
Supporting Agencies
DISB 2017 Enhancement Project of Urbino University
Keywords:
Marine alkaloid, brominated bisindole, chromatin condensation, caspases, bcl-2 proteins, NBD-tagged bisindole.
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How to Cite
Salucci, S., Burattini, S., Buontempo, F., Orsini, E., Furiassi, L., Mari, M., Lucarini, S., Martelli, A. M., & Falcieri, E. (2018). Marine bisindole alkaloid: A potential apoptotic inducer in human cancer cells. European Journal of Histochemistry, 62(2). https://doi.org/10.4081/ejh.2018.2881