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

Autor: Sara Salucci, Sabrina Burattini, Francesca Buontempo, Ester Orsini, Lucia Furiassi, Michele Mari, Simone Lucarini, Alberto M. Martelli, Elisabetta Falcieri
Jazyk: angličtina
Rok vydání: 2018
Předmět:
Zdroj: European Journal of Histochemistry, Vol 62, Iss 2 (2018)
Druh dokumentu: article
ISSN: 1121-760X
2038-8306
DOI: 10.4081/ejh.2018.2881
Popis: 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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