DHPAC, a novel synthetic microtubule destabilizing agent, possess high anti-tumor activity in vincristine-resistant oral epidermoid carcinoma in vitro and in vivo

Zhang, Ying, Gong, Fu-Lian, Lu, Zhen-Ning, Wang, Hong-Yuan, Cheng, Yan-Na, Liu, Zhao-Peng, Yu, Lu-Gang ORCID: 0000-0001-9641-3712, Zhang, Hui-Hui and Guo, Xiu-Li (2017) DHPAC, a novel synthetic microtubule destabilizing agent, possess high anti-tumor activity in vincristine-resistant oral epidermoid carcinoma in vitro and in vivo. INTERNATIONAL JOURNAL OF BIOCHEMISTRY & CELL BIOLOGY, 93. pp. 1-11.

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2017-Guo Int J Biochem Cell Biol ACCEPTED VERSION 1-s2.0-S1357272517302704-main.pdf - Author Accepted Manuscript
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Official URL: http://dx.doi.org/10.1016/j.biocel.2017.10.012

Abstract

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.

Item Type:	Article
Uncontrolled Keywords:	Multidrug-resistance, KB/V cells, Microtubule destabilizing agent, Colchicine binding site, PTEN/Akt/NF-kappa B signal pathway
Depositing User:	Symplectic Admin
Date Deposited:	17 Nov 2017 12:24
Last Modified:	13 Feb 2024 15:08
DOI:	10.1016/j.biocel.2017.10.012
Related URLs:	Author Publisher
URI:	https://livrepository.liverpool.ac.uk/id/eprint/3012358