The vitamin A family can significantly decrease the expression of ERbeta of ERs positive breast cancer cells in the presence or absence of ER ligands and paclitaxel.
Taxanes have high activity against breast cancer cells either as the single agent or in combination with other anticancer compounds. The aim of the study was to determine the effects of vitamin A compounds on the cytotoxic action of paclitaxel and on the expression of ERs in the MCF-7 breast cancer cells. Retinol and beta-carotene, but not retinoids, added to the culture exerted an effect on paclitaxel activity. However, only beta-carotene significantly reduced the percentage of proliferating cells (40.36% +/- 5.64, p < 0.01). We observed that vitamin A and its derivatives combined with paclitaxel and estradiol decreased the percentage of proliferating cells, but only in comparison to estradiol group, whereas retinol and lycopene administered together with paclitaxel and tamoxifen decrease significantly the percentage of proliferatin cells (36.85% +/- 4.71, p < 0.0001 and 37.22% +/- 1.59, p < 0.0001 respectively, compared with paclitaxel group). We have shown that paclitaxel increases the expression of ERalpha and ERbeta mRNA in MCF-7 line. The strongest effect of transcription inhibition ERalpha (2.5 times) and especially ERbeta (10 times) was observed after addition of 9-cis retinoic acid and paclitaxel. This data suggests a synergistic effect of the compounds on ERbeta down-regulation. Our results support the use of retinoid is treatment of ER positive breast cancer patients.
Czeczuga-Semeniuk
Ewa
E
Department of Reproduction and Gynecological Endocrinology, Medical University of Biaystok, 15-276 Białystok, M. Skłodowskiej-Curie 24 A, Poland. czeczuga@wp.pl
Jarzabek
Katarzyna
K
Lemancewicz
Dorota
D
Wołczyński
Sławomir
S