AIMTo investigate the effects of tamoxifen on proliferation of human breast cancer Bcap-37 cells and cervical carcinoma HeLa cells and to explore it's possible mechanism.

METHODSThe techniques of cell culture, growth curves, flow cytometry and laser scanning confocal microscope were used.

RESULTSTamoxifen (10(-6) mol/L) shifted the growth curve of Bcap-37 cells downward, and shifted the growth curve of HeLa cells upward. Tamoxifen (10(-8) - 10(-6) mol/L) inhibited the proliferation of Bcap-37 cells in a dose-dependent manner, but stimulated the proliferation of HeLa cells in a dose-dependent manner. Bcap-37 cells appeared apoptosis when treated with tamoxifen (10(-6) mol/L), and the same dose stimulated the proliferation of HeLa cells at GI/S phases. The apoptotic rate of Bcap-37 cells was 97.5%. It blocked G1 phase of HeLa cells from 55.5% to 32.8%, and increased the S phase from 29.0% to 49.4%. Tamoxifen (10(-6) mol/L) also increased the releasing of calcium in Bcap-37 and HeLa cells.

CONCLUSIONTamoxifen can significantly influence the proliferation of breast cancer and cervical carcinoma cells possibly by affecting cell cycle and stimulating the releasing of Ca2+ in the cells.

Breast Neoplasms ; drug therapy ; pathology ; Cell Proliferation ; drug effects ; Female ; HeLa Cells ; Humans ; Tamoxifen ; pharmacology ; therapeutic use ; Tumor Cells, Cultured ; Uterine Cervical Neoplasms ; drug therapy ; pathology

OBJECTIVETo investigate the potential therapeutic effect of tamoxifen in treating abnormal skin scar contraction.

METHODSFibroblast-populated collagen lattices, which were made by embedding human dermal fibroblasts within type I collagen forming a three-dimensional culture system, were used as an invitro model. Then media either without or with addition of tamoxifen from 1 mumol/L to 50 mumol/L were added to the collagen lattices. Lattice areas were measured at intervals to assess the influence of tamoxifen on the lattice contraction. To visualize changes in the morphology and vitality of fibroblasts, MTT was added to the lattices.

RESULTSTamoxifen had an inhibitory effect on lattice contraction by a dose- and time-dependent pattern. 5 mumol/L or less of tamoxifen didn't show any influence on lattice contraction but 30 mumol/L or higher completely inhibited contraction. At intermediate concentrations from 10 mumol/L to 20 mumol/L the degree of lattice contraction was dose- and time-dependent, which was demonstrated by the reversibility of inhibition. Both the inhibition of contraction and the reversibility of inhibition appeared to correlate with changes in fibroblast morphology.

CONCLUSIONTamoxifen could inhibit the contraction of fibroblast-populated collagen lattices, indicating that tamoxifen may have potential effect on abnormal scar contraction in vivo.

Cicatrix ; drug therapy ; Collagen ; physiology ; Dose-Response Relationship, Drug ; Fibroblasts ; drug effects ; physiology ; Humans ; Skin ; cytology ; drug effects ; Tamoxifen ; pharmacology ; therapeutic use ; Time Factors

Tamoxifen is an antagonist of the estrogen receptor and currently used for the treatment of breast cancer. The current treatment of cutaneous leishmaniasis with pentavalent antimony compounds is not satisfactory. Therefore, in this study, due to its antileishmanial activity, effects of tamoxifen on the growth of promastigotes and amastigotes of Leishmania major Iranian strain were evaluated in vitro. Promastigotes and amastigotes were treated with different concentrations (1, 5, 10, 20, and 50 µg/ml) and time periods (24, 48, and 72 hr) of tamoxifen. After tamoxifen treatment, MTT assay (3-[4,5-dimethylthiazol-2-yl]-2,5 biphenyl tetrazolium bromide assay) was used to determine the percentage of live parasites and Graph Pad Prism software to calculate IC50. Flow cytometry was applied to investigate the induction of tamoxifen-induced apoptosis in promastigotes. The half maximal inhibitory concentration (IC50) of tamoxifen on promastigotes was 2.6 µg/ml after 24 hr treatment. Flow cytometry analysis showed that tamoxifen induced early and late apoptosis in Leishmania promastigotes. While after 48 hr in control group the apoptosis was 2.0%, the 50 µg/L concentration of tamoxifen increased it to 59.7%. Based on the in vitro antileishmanial effect, tamoxifen might be used for leishmaniasis treatment; however, further researches on in vivo effects of tamoxifen in animal models are needed.
Animals ; Antiprotozoal Agents/pharmacology/therapeutic use ; Apoptosis/*drug effects ; Cells, Cultured ; Inhibitory Concentration 50 ; Leishmania major/*drug effects ; Leishmaniasis, Cutaneous/drug therapy ; Macrophages/parasitology ; Mice ; Tamoxifen/*pharmacology/therapeutic use

OBJECTIVETo assess the effect of different schemes of premenopausal tamoxifen therapy on the endometrium.

METHODSTotally 109 normal premenopausal women positive for high-risk factors of breast cancer were divided into two groups, namely periodic and consecutive tamoxifen treatment groups. Endometrial thickness as examined by vaginal sonography was assessed in relation to duration of tamoxifen use and time from discontinuation of the drug.

RESULTSAfter one year of tamoxifen use, the mean endometrial thickness in periodic treatment group was 6.5-/+1.4 mm, and 10.2-/+2.0 mm in consecutive treatment group. Endometrial thickness increased with the duration of tamoxifen use at the rate of 0.51 mm/year in the periodic treatment group, and 0.73 mm/year in consecutive treatment group. After discontinuation of tamoxifen, the endometrial thickness in the former group decreased by 1.29 mm/year, and by 1.33 mm/year in the latter.

CONCLUSIONSEndometrial hyperplasia is obviously milder in premenopausal women receiving periodic tamoxifen treatment who are at risk for breast cancer than that in women with consecutive treatment. After discontinuation of the drug, the endometrial thickness decreases at a roughly equal slow rate in the two groups.

Adult ; Breast Neoplasms ; drug therapy ; Drug Administration Schedule ; Endometrium ; anatomy & histology ; diagnostic imaging ; drug effects ; Female ; Humans ; Premenopause ; drug effects ; Risk ; Tamoxifen ; administration & dosage ; pharmacology ; therapeutic use ; Time Factors ; Ultrasonography

OBJECTIVETo investigate the effect of Evn-50 extracted from Vitex negundo on human breast cancer cell line MCF-7 and MCF-7/TAM-R cells in vitro.

METHODSMCF-7 and tamoxifen-resistant MCF-7/TAM-R cells were treated with Evn-50,tamoxifen or combination of Evn-50 and tamoxifen. Cell proliferation inhibition rates were determined by MTT assay. The apoptosis rate and the change of cell cycle were detected by PI staining flow cytometry. Protein expression of phospho-MAPK 44/42 (Thr202/Tyr204),MAPK P44/42, phospho-AKT (Ser473) and AKT were detected with Western blotting.

RESULTSThe viability of MCF-7 cells was decreased in combination group [(28.65 ±11.43)%] and Evn-50 group [(53.02 ±15.14)%] compared with TAM group (P<0.01). The cell viability of MCF-7/TAM-R in combination group [(42.11 ±14.30)%] was significantly lower than that in TAM group [(92.18 ±13.16)%] (P<0.01). The cell apoptosis rate was dependent on the time of treatment in all groups,the effects on apoptosis and G2/M phase cells were most prominent at 72 h (P<0.01). Western blotting revealed that protein levels of phosphorylated AKT and p-MAPK44/42 decreased,while the expression of total AKT and MAPK44/42 was stable. In MCF-7/TAM-R cells,the expression of phosphorylation of AKT and MAPK44/42 protein was not changed in Evn-50 or TAM alone group,but significantly inhibited in the combination group at 72 h.

CONCLUSIONEvn-50 can inhibit cell growth and induce apoptosis in MCF-7 and MCF-7/TAM-R cells,it can reverse tamoxifen-resistance of MCF-7/TAM-R cells.The mechanisms may be related to the down-regulation of phosphorylated ERK1/2 in MAPK signal pathway and phosphorylated AKT in AKT signal pathway.

Apoptosis ; drug effects ; Breast Neoplasms ; drug therapy ; metabolism ; pathology ; Cell Cycle ; drug effects ; Cell Proliferation ; drug effects ; Drug Resistance, Neoplasm ; drug effects ; Drugs, Chinese Herbal ; pharmacology ; Female ; Humans ; MCF-7 Cells ; Phosphorylation ; Proto-Oncogene Proteins c-akt ; metabolism ; Signal Transduction ; drug effects ; Tamoxifen ; therapeutic use ; Vitex ; chemistry