Estrogen effects on tubulin expression and taxane mediated cytotoxicity in prostate cancer cells
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Updated: Aug 12, 2026
An Orthotopic Murine Model of Human Prostate Cancer Metastasis
Published on: September 19, 2013
R Bruce Montgomery1, Michael Bonham, Peter S Nelson
1Department of Medicine, University of Washington, Seattle, 98108, USA. rbmontgo@u.washington.edu
Background:
The present study was designed to determine if estrogens change microtubule polymerization and modulate cell cycle progression in vitro, related to modulation of tubulin expression and to determine if estrogens had antagonistic or synergistic effects with microtubule active agents.
Methods:
cDNA array analysis of LNCaP cells treated with the estrogens, estradiol, estrone, diethylstilbestrol (DES), and 2-methoxyestradiol (2-ME) was carried out and the results confirmed by PCR and Western blotting. Microtubule arrays in cells treated with estrogens were assessed using indirect immunofluorescence. The effects of combining estrogens with taxane was assessed by MTT assay and flow cytometry for cell cycle kinetics. Human prostate cancer xenografts were treated with DES and docetaxel to assess the effects of combining estrogens and taxane in vivo.
Results:
Treatment of LNCaP cells with DES and 2-ME suppressed transcripts and protein for beta-tubulin isotype IVa. This effect on tubulin synthesis was not blocked by estrogen or androgen receptor modulators. Other estrogens had no effect on beta-tubulin expression. 2-ME and DES decreased the density of microtubules. The administration of DES or 2-ME with paclitaxel enhanced cytotoxicity and G(2)-M arrest in vitro. DES enhanced tumor suppression in a human prostate cancer xenograft model when combined with the taxane docetaxel.
Conclusion:
The use of DES and 2-ME enhances the effects of taxanes and may be a novel and important means of increasing therapeutic efficacy of cytotoxic chemotherapy against prostate carcinoma.
Insights
Certain estrogens, like diethylstilbestrol (DES) and 2-methoxyestradiol (2-ME), enhance chemotherapy by affecting microtubule polymerization and cell cycle progression in prostate cancer cells.
Area of Science:
- Molecular Biology
- Cell Biology
- Cancer Research
Background:
- Estrogens' role in cell cycle progression and microtubule dynamics is not fully understood.
- Investigating estrogen interactions with microtubule-targeting agents is crucial for cancer therapy.
Purpose of the Study:
- To determine if estrogens alter microtubule polymerization and cell cycle progression.
- To examine estrogen effects on tubulin expression.
- To assess estrogen interactions with microtubule-active agents in prostate cancer.
Main Methods:
- LNCaP cells and prostate cancer xenografts were treated with various estrogens (estradiol, estrone, diethylstilbestrol (DES), 2-methoxyestradiol (2-ME)) and taxanes.
- Techniques included cDNA array, PCR, Western blotting, immunofluorescence, MTT assay, and flow cytometry.
Main Results:
- DES and 2-ME suppressed beta-tubulin isotype IVa expression and decreased microtubule density.
- Combining DES or 2-ME with paclitaxel increased cytotoxicity and G(2)-M arrest in vitro.
- DES combined with docetaxel showed enhanced tumor suppression in vivo.
Conclusions:
- Diethylstilbestrol (DES) and 2-methoxyestradiol (2-ME) enhance taxane efficacy in prostate cancer.
- These estrogens may offer a novel approach to improve cytotoxic chemotherapy for prostate carcinoma.
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