Open AccessNovel hydrophilic docetaxel ( CQMU ‐0519) analogue inhibits proliferation and induces apoptosis in human A 549 lung, SKVO 3 ovarian and MCF 7 breast carcinoma cell lines
Author(s) -
Fauzee N. J. S.,
Wang Y.L.,
Dong Z.,
Li Q.G.,
Wang T.,
Mandarry M. T.,
Xu L.,
Pan J.
Publication year - 2012
Publication title -
cell proliferation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.647
H-Index - 74
eISSN - 1365-2184
pISSN - 0960-7722
DOI - 10.1111/j.1365-2184.2012.00825.x
Subject(s) - docetaxel , apoptosis , mcf 7 , cell cycle , cell growth , cancer research , cell culture , biology , microbiology and biotechnology , pharmacology , medicine , cancer , cancer cell , biochemistry , genetics , human breast
Objective Objectives of this investigation were not merely to perform a comparative study with original docetaxel, but to define anti‐proliferative and apoptotic effects of novel hydrophilic docetaxel ( CQMU ‐0519) analogue on A 549 lung, SKVO 3 ovary and MCF 7 breast carcinoma cell lines. Materials and methods The materials for the study consist of a completely new docetaxel analogue ( CQMU ‐0519), synthesized by the Department of Pharmacology, Chongqing Medical University, China, which is completely soluble in water. 50 n m of drug concentration was utilized on all three cell lines where cell population growth was assessed using cell culture kit‐8 and flow cytometry analysis, whereas apoptotic pathways were unveiled by use of annexin‐V FITC , apoptosis DNA ladder, caspases‐3, 6, 8 and 9; in the meanwhile, regulation of Bcl‐2 family members was analysed by western blotting. Result The novel docetaxel analogue ( CQMU ‐0519) suppressed cell proliferation in all three cell lines, inhibition of cell proliferation and cell cycle arrest being more evident in G 2 /M phase. Also, in both lung and ovarian cell lines, apoptotic levels were higher as measured by the various tests performed, and downregulation of Bcl‐2 and Bcl‐xL with increased expressions of Bad and Bax indicated the intrinsic pathway for apoptosis. Nevertheless, it was found that MCF 7 cells, although also manifesting high levels of apoptosis, used the extrinsic pathway instead. Hence, it was shown that novel docetaxel analogue ( CQMU ‐0519) may have some prospective use in future clinical trials. Conclusions Novel hydrophilic docetaxel analogue ( CQMU ‐0519) inhibited cell proliferation and enhanced the intrinsic apoptotic pathway in lung and ovarian carcinoma cells, whereas it used the extrinsic one in breast adenocarcinoma cells.