A new HDAC inhibitor cinnamoylphenazine shows antitumor activity in association with intensive macropinocytosis.
Oncotarget
; 8(9): 14748-14758, 2017 Feb 28.
Article
em En
| MEDLINE
| ID: mdl-28107195
ABSTRACT
Previous studies have shown that intensive macropinocytosis occurs in cancer cells and neutral red (NR) is noted for its capability to enter into the cell massively through a process mimetic to macropinocytosis. In addition, trans-cinnamic acid (tCA) has been found to be an inhibitor of histone deacetylase (HDAC). In the present study, cinnamoylphenazine (CA-PZ) that consists of NR and tCA moieties was synthesized and evaluated. As shown, CA-PZ massively entered into colon carcinoma HT-29 cells and pancreatic carcinoma MIA PaCa-2 cells and this entry was blocked by 5-(N-ethyl-N-isopropyl) amiloride (EIPA, an inhibitor of macropinocytosis), indicating a macropinocytosis-mediated uptake. Furthermore, CA-PZ markedly increased the protein expression levels of acetyl-H3, acetyl-H4 and p21 in HT-29 cells and MIA PaCa-2 cells. CA-PZ significantly inhibited the growth of colon carcinoma HT-29 and pancreatic carcinoma MIA PaCa-2 xenografts. By in vivo imaging, CA-PZ displayed prominent accumulation in the tumor xenografts. The study indicates that the newly synthesized CA-PZ acts as an HDAC inhibitor in association with intensive macropinocytosis-mediated intracellular delivery in cancer cells. The use of neutral red for preparation of chimeric molecules with the attribute of macropinocytosis-mediated intracellular delivery might open an alternative way for development of HDAC inhibitors.
Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Neoplasias Pancreáticas
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Fenazinas
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Pinocitose
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Cinamatos
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Neoplasias do Colo
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Ensaios Antitumorais Modelo de Xenoenxerto
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Inibidores de Histona Desacetilases
Tipo de estudo:
Risk_factors_studies
Limite:
Animals
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Female
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Humans
Idioma:
En
Revista:
Oncotarget
Ano de publicação:
2017
Tipo de documento:
Article
País de afiliação:
China