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Prostate cancer cell growth inhibition by tamoxifen is associated with inhibition of protein kinase C and induction of p21(waf1/cip1).
- Source :
-
The Prostate [Prostate] 1998 Sep 15; Vol. 37 (1), pp. 51-9. - Publication Year :
- 1998
-
Abstract
- Background: Inhibition of protein kinase C (PKC) and modulation of transforming growth factor-beta (TGF-beta) are both associated with tamoxifen treatment, and both appear to be important in the regulation of prostate cancer cell growth. Investigations were performed which sought to measure the efficacy, and to elucidate the mechanism of growth inhibition by tamoxifen, in hormone-refractory prostate cancer.<br />Methods: Growth assays were performed on PC3, PC3-M, and DU145 prostate cancer cells. TGF-beta was measured by ELISA; p21(waf1/cip1) and retinoblastoma (Rb) protein levels were measured by Western blot; PKC activity was measured by kinase assay; and effects upon cell cycle were measured by flow cytometric analysis.<br />Results: IC50s for growth inhibition ranged from 5.5-10 microM, and were not affected by estrogen. Tamoxifen-mediated growth inhibition was not associated with induction of TGF-beta. However, tamoxifen treatment was associated with inhibition of PKC, which was followed by induction of p21(waf1/cip1), Rb dephosphorylation, and G1/S phase cell cycle arrest. Similar effects were observed with the known PKC inhibitor, Ro31-8220.<br />Conclusions: These data suggest that micromolar concentrations of tamoxifen inhibit prostate cancer cell growth by inhibition of PKC, resulting in induction of the p21(waf1/cip1) protein.
- Subjects :
- Antineoplastic Agents, Hormonal administration & dosage
Cell Division drug effects
Cyclin-Dependent Kinase Inhibitor p21
Cyclins biosynthesis
Dose-Response Relationship, Drug
Humans
In Vitro Techniques
Male
Prostatic Neoplasms enzymology
Protein Kinase C biosynthesis
Signal Transduction
Tamoxifen administration & dosage
Transforming Growth Factor beta biosynthesis
Antineoplastic Agents, Hormonal pharmacology
Cyclins drug effects
Prostatic Neoplasms drug therapy
Protein Kinase C drug effects
Tamoxifen pharmacology
Transforming Growth Factor beta drug effects
Subjects
Details
- Language :
- English
- ISSN :
- 0270-4137
- Volume :
- 37
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- The Prostate
- Publication Type :
- Academic Journal
- Accession number :
- 9721069
- Full Text :
- https://doi.org/10.1002/(sici)1097-0045(19980915)37:1<51::aid-pros8>3.0.co;2-b