An emerging new class of targeted therapeutic molecules against the enzyme fatty acid amide hydrolase (FAAH) is a novel series of pyrrolo-1,5-benzoxa(thia) zepine compounds. A member of this family, pyrrolo-1,5-benzoxazepine-15 (PBOX-15), is a tubulin depolymerizing agent displaying a proapoptotic activity in a variety of human tumor cell types, including those derived from both solid and hemato-logical malignancies, with minimal toxicity towards normal blood and bone marrow cells. In this study, we evaluated the PBOX-15-mediated effects in human colorectal cancer cell (CRC) lines. The compound, used at doses equal to or greater than 1 μM inhibits the proliferation of human CRC cell lines in a dose- and time-dependent manner, inducing a significant cell cycle arrest in the G2/M phase. DNA fragmentation assays and western blot analysis demonstrated that treatments prolonged over 48 h triggered a strong activation of the intrinsic apoptotic pathway as indicated by activation of caspase-3, caspase-9 and PARP. Moreover, nanomolar doses of PBOX-15, unable to cause microtubule depolymer-ization, significantly improved the oxaliplatin and 5-fluouracil-induced anti-proliferative effects in CRC cell lines. These results showed, for the first time, that PBOX-15 represents a promising compound for the treatment of human CRC and a strong candidate for novel therapeutic options. © 2013 Elsevier B.V. All rights reserved.

Gangemi, G., Gazzerro, P., Fiore, D., Proto, M.C., Butini, S., Gemma, S., et al. (2013). PBOX-15 induces apoptosis and improves the efficacy of oxaliplatin in human colorectal cancer cell lines. EUROPEAN JOURNAL OF PHARMACOLOGY, 714(1-3), 379-387 [10.1016/j.ejphar.2013.07.011].

PBOX-15 induces apoptosis and improves the efficacy of oxaliplatin in human colorectal cancer cell lines

Butini, Stefania;Gemma, Sandra;Casagni, Alice;Campiani, Giuseppe;
2013-01-01

Abstract

An emerging new class of targeted therapeutic molecules against the enzyme fatty acid amide hydrolase (FAAH) is a novel series of pyrrolo-1,5-benzoxa(thia) zepine compounds. A member of this family, pyrrolo-1,5-benzoxazepine-15 (PBOX-15), is a tubulin depolymerizing agent displaying a proapoptotic activity in a variety of human tumor cell types, including those derived from both solid and hemato-logical malignancies, with minimal toxicity towards normal blood and bone marrow cells. In this study, we evaluated the PBOX-15-mediated effects in human colorectal cancer cell (CRC) lines. The compound, used at doses equal to or greater than 1 μM inhibits the proliferation of human CRC cell lines in a dose- and time-dependent manner, inducing a significant cell cycle arrest in the G2/M phase. DNA fragmentation assays and western blot analysis demonstrated that treatments prolonged over 48 h triggered a strong activation of the intrinsic apoptotic pathway as indicated by activation of caspase-3, caspase-9 and PARP. Moreover, nanomolar doses of PBOX-15, unable to cause microtubule depolymer-ization, significantly improved the oxaliplatin and 5-fluouracil-induced anti-proliferative effects in CRC cell lines. These results showed, for the first time, that PBOX-15 represents a promising compound for the treatment of human CRC and a strong candidate for novel therapeutic options. © 2013 Elsevier B.V. All rights reserved.
2013
Gangemi, G., Gazzerro, P., Fiore, D., Proto, M.C., Butini, S., Gemma, S., et al. (2013). PBOX-15 induces apoptosis and improves the efficacy of oxaliplatin in human colorectal cancer cell lines. EUROPEAN JOURNAL OF PHARMACOLOGY, 714(1-3), 379-387 [10.1016/j.ejphar.2013.07.011].
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11365/45154
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