DHPAC, a novel synthetic microtubule destabilizing agent, possess high anti-tumor activity in vincristine-resistant oral epidermoid carcinoma in vitro and in vivo
| Autor: | Hui-Hui Zhang, Ying Zhang, Hong-Yuan Wang, Zhen-Ning Lu, Lu-Gang Yu, Yan-Na Cheng, Fu-Lian Gong, Xiu-Li Guo, Zhao-Peng Liu |
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| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Cell Antineoplastic Agents Apoptosis Biochemistry 03 medical and health sciences 0302 clinical medicine In vivo medicine Humans PTEN Protein kinase B Membrane Potential Mitochondrial Cyclin-dependent kinase 1 biology Cell growth Cell Biology Molecular biology Tubulin Modulators Neoplasm Proteins 030104 developmental biology medicine.anatomical_structure Epidermoid carcinoma Drug Resistance Neoplasm Vincristine 030220 oncology & carcinogenesis Carcinoma Squamous Cell MCF-7 Cells biology.protein Mouth Neoplasms K562 Cells |
| Zdroj: | INTERNATIONAL JOURNAL OF BIOCHEMISTRY & CELL BIOLOGY |
| ISSN: | 1357-2725 |
| DOI: | 10.1016/j.biocel.2017.10.012 |
| Popis: | Multidrug resistance (MDR) is one of major obstacles to effective chemotherapeutic treatment of cancer. This study showed that DHPAC, 2-(6-ethoxy-3-(3-ethoxyphenylamino) -1-methyl-1,4-dihydroindeno[1,2-c]pyrazol-7-yloxy) acetamide, a novel compound that binds to the same site on microtubules as colchicine, has high anti-tumour activity in vincristine-resistant oral epidermoid carcinoma (KB/V) cells. It found that the presence of DHPAC strongly inhibited KB/V cell growth in vivo and in mice xenograft. The inhibitory effect of DHPAC is much stronger than that by colchicine in these KB/V cells (IC50: 64.4nM and 458.0nM respectively). Treatment of the cells with DHPAC induced cell apoptosis by reducing mitochondrial membrane potential and altered the expression of several apoptosis-related proteins such as Bcl-2, Bax, Caspase-9, Cytochrome c and PARP. DHPAC treatment also caused cell rest in G2/M phase by regulating of the expression of a number of cell cycle-related proteins (e.g. Cyclin B1, Cdc2, Cdc25b, Cdc25c, RSK2). Furthermore, DHPAC presence inhibits PTEN phosphorylation and PTEN/Akt/NF-κB signalling. Thus, DHPAC has potent anti-cancer activity in MDR tumuors and may be a potential therapeutic agent for the treatment of vincristine-resistant human oral epidermoid carcinoma. |
| Databáze: | OpenAIRE |
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