Abstract：
:Microtubules are critical elements that are involved in a wide range of cellular processes, and thus, they have become an attractive target for many anticancer drugs. A novel synthesised compound, 12P, was identified as new microtubule inhibitor. This compound inhibits tubulin polymerisation through binding to the colchicine-binding site of tubulin. 12P exhibits excellent anti-proliferative activities against a panel of human cancer cell lines, with IC₅₀ values range from 9 to 55nM. Interestingly, compound 12P also displayed equally potent cytotoxicity against several drug-resistant cell lines, and it showed high selectivity for active human umbilical vein endothelial cells (HUVECs). Further flow cytometric analysis showed that 12P induces G₂/M phase arrest and apoptosis in A549 cells. Cellular studies have revealed that the induction of apoptosis by 12P was associated with a collapse of mitochondrial membrane potential (MMP), accumulation of reactive oxygen species (ROS), alterations in the expression of some cell cycle-related proteins (e.g. Cyclin B1, Cdc25c, Cdc2) and some apoptosis-related proteins (e.g. Bax, Bad, Bcl-2, Bcl-xl). Importantly, 12P significantly reduced the growth of xenograft tumours of A549 cells in vivo (tumour inhibitory rate of 12P: 84.2%), without any loss of body weight. Taken together, these in vitro and in vivo results suggested that 12P may become a promising lead compound for the development of new anticancer drugs.
journal_name
Biochem Pharmacoljournal_title
Biochemical pharmacologyauthors
Yan J,Pang Y,Sheng J,Wang Y,Chen J,Hu J,Huang L,Li Xdoi
10.1016/j.bcp.2015.07.008subject
Has Abstractpub_date
2015-09-01 00:00:00pages
51-61issue
1eissn
0006-2952issn
1873-2968pii
S0006-2952(15)00378-0journal_volume
97pub_type
杂志文章abstract：:Basic fibroblast growth factor (bFGF) preserves the viability of at least 13 different cells, including epithelial, endothelial, smooth muscle and neuronal cells. In spite of this profound and rather universal effect on cell viability, detailed studies regarding the mechanism of bFGF's action have not been conducted. ...
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pub_type： 杂志文章
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pub_type： 杂志文章
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pub_type： 杂志文章
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pub_type： 杂志文章
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pub_type： 杂志文章
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journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/j.bcp.2003.10.034
更新日期：2004-03-15 00:00:00
