Novel hydrophilic docetaxel (CQMU-0519) analogue inhibits proliferation and induces apoptosis in human A549 lung, SKVO3 ovarian and MCF7 breast carcinoma cell lines.

Abstract

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 A549 lung, SKVO3 ovary and MCF7 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 nm 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 MCF7 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.

• Authors: N J S Fauzee, Y-L Wang, Z Dong, Q-G Li, T Wang, M T Mandarry, L Xu, J Pan
• Journal: Cell proliferation (Cell Prolif) Vol. 45 Issue 4 Pg. 352-64 (Aug 2012) ISSN: 1365-2184 [Electronic] England
• PMID: 22672263 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2012 Blackwell Publishing Ltd.

Chemical References

• Antineoplastic Agents
• Proto-Oncogene Proteins c-bcl-2
• Taxoids
• Docetaxel
• Poly(ADP-ribose) Polymerases
• Caspases

Topics

• Antineoplastic Agents (pharmacology)
• Apoptosis (drug effects)
• Blotting, Western
• Breast Neoplasms (pathology)
• Caspases (metabolism)
• Cell Line, Tumor
• Colorimetry
• Docetaxel
• Enzyme Activation
• Female
• Humans
• Lung Neoplasms (pathology)
• Ovarian Neoplasms (pathology)
• Poly(ADP-ribose) Polymerases (metabolism)
• Proto-Oncogene Proteins c-bcl-2 (metabolism)
• Taxoids (chemistry, pharmacology)