Can vitamin A modify the activity of docetaxel in MCF-7 breast cancer cells?
Docetaxel is one of the most effective chemotherapeutic agents in the treatment of breast cancer. On the other hand, the vitamin A family compounds play the essential roles in many biological processes in mammary gland. The aim of our study was to investigate the effect of all-trans retinol, carotenoids (beta-carotene, lycopene) and retinoids (9-cis, 13-cis and all-trans retinoic acid) on the activity of docetaxel and to compare these effects with the estradiol and tamoxifen actions on human ER(+) MCF-7 breast cancer cell line. The evaluation was based on [3H] thymidine incorporation and the proliferative activity of PCNA and Ki 67 positive cells. In our study, the incorporation of [3H] thymidine into cancer cells was inhibited to 50% by 0.2, 0.5 and 1 microM of docetaxel in the 24-hour culture and addition of estradiol (0.001 microM) didn't influence the results. However, addition of tamoxifen caused a statistically significant decrease of the percentage of the proliferating cells in the culture medium with 0.2 and 0.5 microM of docetaxel (38.99 +/- 2.84%, p<0.01 and 40.67 +/- 5.62%, p<0.01) in comparison to the docetaxel only group. The above-mentioned observations were also confirmed with the use of the immunohistochemical investigations. Among the examined vitamin A family compounds, the simultaneous application of beta-carotene (0.1 microM) and docetaxel (0.2 microM) resulted in a statistically significant reduction in the percentage of proliferating cells (40.25 +/- 14.62%, p<0.01). Lycopene (0.1 microM), which stimulates the growth of breast cancer cells in a 24-hour culture, had an inhibitory effect (42.97 +/- 9.58%, p<0.01) when combined with docetaxel (0.2 microM). Although, beta-carotene and lycopene belong to the different chemical groups, they surprisingly had a similar inhibitory influence on both growth and proliferation of MCF-7 breast cancer cells when combined with docetaxel. The application of docetaxel either with beta-carotene or lycopene had comparable inhibitory effect on breast cells growth and proliferation as tamoxifen. Therefore, it may suggest a possible important role of these carotenoids in the breast cancer therapy in women especially when docetaxel is applied.
Czeczuga-Semeniuk
Ewa
E
Department of Reproduction and Gynecological Endocrinology, Medical University of Białystok, Białystok, Poland. czeczuga@wp.pl
Lemancewicz
Dorota
D
Wolczyński
Slawomir
S
D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology; D002338:Carotenoids / Q000494:pharmacology; D049109:Cell Proliferation / Q000187:drug effects; D000077143:Docetaxel; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D004958:Estradiol / Q000494:pharmacology; D006801:Humans; D007150:Immunohistochemistry; D012176:Retinoids / Q000494:pharmacology; D013629:Tamoxifen / Q000494:pharmacology; D043823:Taxoids / Q000494:pharmacology*; D014407:Tumor Cells, Cultured; D014801:Vitamin A / Q000494:pharmacology*
D012176:Retinoids; D043823:Taxoids; D013629:Tamoxifen; D014801:Vitamin A; D000077143:Docetaxel; D002338:Carotenoids; D004958:Estradiol