Estrogen effects on tubulin expression and taxane mediated cytotoxicity in prostate cancer cells.

Article Details

Citation

Montgomery RB, Bonham M, Nelson PS, Grim J, Makary E, Vessella R, Stahl WL

Estrogen effects on tubulin expression and taxane mediated cytotoxicity in prostate cancer cells.

Prostate. 2005 Oct 1;65(2):141-50.

PubMed ID
15924336 [ View in PubMed
]
Abstract

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.

DrugBank Data that Cites this Article

Pharmaco-transcriptomics
DrugDrug GroupsGeneGene IDChangeInteractionChromosome
2-MethoxyestradiolInvestigationalTUBB4A10382
downregulated
2-methoxyestradiol results in decreased expression of TUBB4A mRNA alternative form19p13.3
DiethylstilbestrolApproved Investigational WithdrawnTUBB4A10382
downregulated
Diethylstilbestrol results in decreased expression of TUBB4A mRNA alternative form19p13.3