Antitumor effect of pyrrolo-1,5-benzoxazepine-15 and its synergistic effect with Oxaliplatin and 5-FU in colorectal cancer cells
| Autor: | Maria Proto, Alice Casagni, D. Clive Williams, Antonio Christian Pagano Zottola, Mario Vitale, Daniela M. Zisterer, Vincenzo Di Marzo, Paola Picardi, Chiara Laezza, Donatella Fiore, Stefania Butini, Maurizio Bifulco, Patrizia Gazzerro, Giuseppe Campiani, Simona Pisanti, Alessia Ligresti, Sandra Gemma, Seema M. Nathwani |
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| Přispěvatelé: | Fiore, Donatella, Proto, MARIA CHIARA, Pisanti, Simona, Picardi, Paola, PAGANO ZOTTOLA, ANTONIO CHRISTIAN, Butini, Stefania, Gemma, Sandra, Casagni, Alica, Laezza, Chiara, Vitale, Mario, Ligresti, Alessia, Di Marzo, Vincenzo, Zisterer, Daniela M, Nathwanid, Seema, Williams, Cleeve D, Campiani, Giuseppe, Gazzerro, Patrizia, Bifulco, Maurizio |
| Jazyk: | angličtina |
| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Cancer Research Cell cycle checkpoint Organoplatinum Compounds Colorectal cancer Cell 5-benzoxazepine Apoptosis Pharmacology 0302 clinical medicine Antineoplastic Combined Chemotherapy Protocols Medicine Drug Synergism Keywords Pyrrolo-1 medicine.anatomical_structure Oncology pyrrolo-1 030220 oncology & carcinogenesis Molecular Medicine Fluorouracil Colorectal Neoplasms HT29 Cells medicine.drug Research Paper Cell type 5-Fluorouracil FAAH inhibitors colorectal cancer 03 medical and health sciences combinatorial effect oxaliplatin pyrrolo-1 5-benzoxazepine Cell Line Tumor Humans Pyrroles Cell Proliferation Oxaliplatin Pyrrolo-1 business.industry Cell growth Cell Cycle Checkpoints medicine.disease Oxazepines 030104 developmental biology Cell culture Pyrrolo-1 5-benzoxazepine business |
| Zdroj: | Cancer biology & therapy (Online) (2015). doi:10.1080/15384047.2015.1078028 info:cnr-pdr/source/autori:Fiore D, Proto MC, Pisanti S, Picardi P, Pagano Zottola AC, Butini S, Gemma S, Casagni A, Laezza C, Vitale M, Ligresti A, Di Marzo V, Zisterer DM, Nathwani S, Williams DC, Campiani G, Gazzerro P, Bifulco M./titolo:Antitumor effect of pyrrolo-1,5-benzoxazepine-15 and its synergistic effect with Oxaliplatin and 5-FU in colorectal cancer cells./doi:10.1080%2F15384047.2015.1078028/rivista:Cancer biology & therapy (Online)/anno:2015/pagina_da:/pagina_a:/intervallo_pagine:/volume Cancer biology & therapy (2015). info:cnr-pdr/source/autori:Fiore D1, Proto MC1, Pisanti S1, Picardi P1, Pagano Zottola AC1, Butini S2, Gemma S2, Casagni A2, Laezza C3, Vitale M4, Ligresti A5, Di Marzo V5, Zisterer DM6, Nathwani S6, Williams DC6, Campiani G2, Gazzerro P1, Bifulco M4./titolo:Antitumor effect of pyrrolo-1,5-benzoxazepine-15 and its synergistic effect with Oxaliplatin and 5-FU in colorectal cancer cells./doi:/rivista:Cancer biology & therapy (Print)/anno:2015/pagina_da:/pagina_a:/intervallo_pagine:/volume |
| DOI: | 10.1080/15384047.2015.1078028 |
| Popis: | Some compounds of a series of novel pyrrolo-1,5-benzoxa(thia)zepine, a well-known group of tubulin targeting agents, display anti-tumour effects mainly inducing cell cycle arrest and apoptosis in several human cancer models. A member of this family, pyrrolo-1,5-benzoxazepine-15 (PBOX-15), has previously shown potent pro-apoptotic activity in a variety of human tumor cell types, 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, DLD-1 and HT-29. The compound, used at concentrations equal to or greater than 1?M, inhibited the proliferation of human CRC cells, inducing a significant cell cycle arrest in the G2/M phase. In DLD-1 cells, treatments prolonged over 48 h triggered a strong activation of the intrinsic apoptotic pathway as indicated by activation of caspase-9, caspase-3 and PARP cleavage. Moreover, nanomolar concentrations of PBOX-15, significantly improved the oxaliplatin and 5-fluouracil-induced anti-proliferative effects in DLD1 cell line. The observed synergistic interaction of both PBOX-15/Oxaliplatin and PBOX-15/5FU may involve activation of p38 MAPK and JNK pathway, which in turn significantly increased caspase-3 cleavage in DLD-1 cells, treated with PBOX-5/Oxaliplatin but not with PBOX-15/5FU. Moreover, PBOX-15/5FU-treated cells showed an increase in expression of the pro-apoptotic protein Bax. Taken together, these results show that PBOX-15 could represent a promising compound for the treatment of human CRC and a strong candidate for novel therapeutic options. |
| Databáze: | OpenAIRE |
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