Response rates of tumours to docetaxel (DOCT) are 45-60% in advanced breast cancer but problems associated with side effects, drug resistance and high costs occur. Conjugated linoleic acids (CLAs) also have anti-tumorigenic activity that elicits similar changes in oncogene expression to DOCT and could augment DOCT efficacy. CLA isomers appear to differ in cytotoxicity toward cancer cells. Effects of two CLA isomers on cytotoxicity of DOCT in breast cancer cells (MCF-7; MDA-MB-231) in vitro were assessed. Cells were incubated up to 72h with 40 mu M each of LA or CLA isomers (cis-9, trans-10 CLA, or trans-10, cis-12 CLA) or a 50:50 isomer mix, alone or with DOCT (0-64 mu M); a pilot study determined IC50 and IC70 concentrations. Treatments were concurrent (CLA and DOCT together) or sequential (CLA then DOCT). MTT assay determined cell viability. Trans-10, cis-12 CLA was the most effective fatty acid (P<0.001) and increased with treatment time. IC50 and IC70 concentrations of DOCT were determined, concurrently or sequentially, with and without fatty acids, in the two cell types. Concurrent treatment with trans-10, cis-12 CLA and DOCT augmented inhibition of cell growth in one or both cell lines (decreased IC50 and IC70 in MCF-7; P<0.05 but only IC50 in MDA-MB-231; P<0.05). CLA mix reduced IC50 and IC70 in MDA-MB-231 (P<0.001) but not in MCF-7. Cis-9, trans-11 CLA and LA had no effect. Sequential treatment with CLAs then DOCT reduced IC50 and IC70 in MCF-7 but not in MDA-MB-231. The latter had increased IC50 and IC70 with LA treatment (P<0.05) and increased IC70 with cis-9, trans-11 CLA (P<0.05) with sequential but not concurrent treatment. Longer pre-incubation times with trans-10, cis-12 CLA(24-72 h) elicited greater reductions in IC50 and IC70 in MCF-7 cells. Results show that CLA isomers augment anti-tumour effects of docetaxel in breast cancer cells and suggest possible dual treatment regimens. (C) 2007 Elsevier Ltd. All rights reserved.
|Number of pages||10|
|Journal||Prostaglandins, Leukotrienes and Essential Fatty Acids|
|Publication status||Published - Aug 2007|
- inhibits proliferation