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[PMID]: | 28927789 |
[Au] Autor: | Takahashi N; Koyama S; Hasegawa S; Yamasaki M; Imai M |
[Ad] Endereço: | Laboratory of Physiological Chemistry, Institute of Medicinal Chemistry, Hoshi University, 2-4-41 Ebara, Shinagawa, Tokyo 142-8501, Japan. Electronic address: t-noriko@hoshi.ac.jp. |
[Ti] Título: | Anticancer efficacy of p-dodecylaminophenol against high-risk and refractory neuroblastoma cells in vitro and in vivo. |
[So] Source: | Bioorg Med Chem Lett;27(20):4664-4672, 2017 10 15. | [Is] ISSN: | 1464-3405 |
[Cp] País de publicação: | England |
[La] Idioma: | eng |
[Ab] Resumo: | Neuroblastoma is an aggressive and drug-resistant refractory cancer. The human high-risk neuroblastoma cell line, SK-N-AS (non-amplified N-myc) is derived from stromal cells and it is resistant to treatment with retinoic acid (1, RA), which is a chemotherapeutic agent used to induce neuronal cellular differentiation of neuroblastomas. We have developed p-dodecylaminophenol (3, p-DDAP), based on N-(4-hydroxyphenyl)retinamide (2, 4-HPR), a synthetic amide of 1, since 1 and 2 are associated with the side-effect of nyctalopia. In order to evaluate the effects of 3 on high-risk neuroblastomas, we employed SK-N-AS cells as well asa second high-risk human neuroblastoma cell line, IMR-32, which is derived from neuronal cells (amplified N-myc, drug sensitive). Compound 3 suppressed cell growth of SK-N-AS and IMR-32 cells more effectively than 1, 2, p-decylaminophenol (4, p-DAP), N-(4-hydroxyphenyl)dodecananamide (5, 4-HPDD) or N-(4-hydroxyphenyl)decananamide (6, 4-HPD). In SK-N-AS cells, 3 induced G /G arrest and apoptosis to a greater extent than 1 and 2. In IMR-32 cells, 3 induced apoptosis to a similar extent as 1 and 2, potentially by inhibiting N-myc expression. In addition, i.p. administration of 3 suppressed tumor growth in SK-N-AS-implanted mice in vivo. Since 3 showed no effects on blood retinol concentrations, in contrast to reductions following the administration of 2, it exhibited excellent anticancer efficacy against high-risk neuroblastoma SK-N-AS and IMR-32 expressing distinct levels of N-myc. Compound 3 may have potential for clinical use in the treatment of refractory neuroblastoma with reduced side effects. |
[Mh] Termos MeSH primário: |
Aminofenóis/química Aminofenóis/farmacologia Antineoplásicos/química Antineoplásicos/farmacologia Apoptose/efeitos dos fármacos
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[Mh] Termos MeSH secundário: |
Aminofenóis/uso terapêutico Animais Antineoplásicos/uso terapêutico Caspase 3/metabolismo Linhagem Celular Tumoral Pontos de Checagem da Fase G1 do Ciclo Celular/efeitos dos fármacos Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos Seres Humanos Masculino Camundongos Camundongos Nus Proteína Proto-Oncogênica N-Myc/genética Proteína Proto-Oncogênica N-Myc/metabolismo Neuroblastoma/tratamento farmacológico Neuroblastoma/metabolismo Neuroblastoma/patologia Proteínas Proto-Oncogênicas c-bcl-2/genética Proteínas Proto-Oncogênicas c-bcl-2/metabolismo Transplante Heterólogo
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[Pt] Tipo de publicação: | JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T |
[Nm] Nome de substância:
| 0 (4-dodecylaminophenol); 0 (Aminophenols); 0 (Antineoplastic Agents); 0 (N-Myc Proto-Oncogene Protein); 0 (Proto-Oncogene Proteins c-bcl-2); EC 3.4.22.- (Caspase 3) |
[Em] Mês de entrada: | 1711 |
[Cu] Atualização por classe: | 171125 |
[Lr] Data última revisão:
| 171125 |
[Sb] Subgrupo de revista: | IM |
[Da] Data de entrada para processamento: | 170921 |
[St] Status: | MEDLINE |
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