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The vitamin A family can significantly decrease the expression of ERbeta of ERs positive breast cancer cells in the
Ewa Czeczuga-Semeniuk1, Katarzyna Jarzabek, Dorota Lemancewicz
1Department of Reproduction and Gynecological Endocrinology, Medical University of Biaystok, 15-276 Białystok, M. Skłodowskiej-Curie 24 A, Poland. czeczuga@wp.pl
Abstract:
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.
Insights
Vitamin A compounds, particularly beta-carotene, enhance paclitaxel
Area of Science:
- Oncology
- Molecular Biology
- Biochemistry
Background:
- Taxanes, such as paclitaxel, are effective in treating breast cancer.
- Estrogen receptors (ERs) play a crucial role in the development of ER-positive breast cancer.
- Vitamin A compounds (retinoids) are being investigated for their potential role in cancer therapy.
Purpose of the Study:
- To investigate the impact of vitamin A compounds on the cytotoxic effects of paclitaxel.
- To examine how vitamin A compounds influence estrogen receptor (ER) expression in breast cancer cells.
- To evaluate the combined effects of vitamin A derivatives, paclitaxel, and hormonal therapies (estradiol, tamoxifen) on cell proliferation.
Main Methods:
- Culturing MCF-7 breast cancer cells.
- Treating cells with paclitaxel, various vitamin A compounds (retinol, beta-carotene, retinoids, lycopene), estradiol, and tamoxifen.
- Assessing cell proliferation using cell counting.
- Quantifying estrogen receptor alpha (ERalpha) and ERbeta messenger RNA (mRNA) expression using quantitative PCR.
Main Results:
- Beta-carotene and retinol, but not other retinoids, modulated paclitaxel's activity.
- Beta-carotene significantly reduced the percentage of proliferating cells.
- Combinations of vitamin A derivatives with paclitaxel and tamoxifen significantly decreased cell proliferation compared to paclitaxel alone.
- Paclitaxel increased ERalpha and ERbeta mRNA expression.
- 9-cis retinoic acid combined with paclitaxel demonstrated the strongest inhibition of ERalpha and ERbeta mRNA transcription, suggesting synergistic down-regulation of ERbeta.
Conclusions:
- Certain vitamin A compounds, notably beta-carotene, can enhance the anti-cancer effects of paclitaxel in breast cancer cells.
- Vitamin A derivatives, particularly 9-cis retinoic acid, can synergistically down-regulate estrogen receptor beta expression when combined with paclitaxel.
- These findings support the potential therapeutic use of retinoids in combination with standard treatments for estrogen receptor-positive breast cancer.
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