Abstract
Purpose: To investigate the effects of tamoxifen and tanshinone administered individually or in combination, on the proliferation of breast cancer (BC) cells, and the underlying mechanism(s) of action.
 Methods: Human breast cancer cell lines (SNU-306, SNU-334 and SNU-1528), and normal primary mammary epithelial cell line (HMEC) were cultured at 37 °C in Dulbecco's modified Eagle's medium (DMEM) supplemented with 5 % fetal bovine serum (FBS), l glutamine (2 mM), penicillin (100 U/ml) and streptomycin (100 μg/ml) in a humidified incubator containing 5 % CO2. Cell proliferation was determined using MTT assay, while real-time quantitative polymerase chain reaction (qRT-PCR) was used to determine the expressions of apoptosis-related genes. The expressions of p38 mitogenactivated protein kinases (p38 MAPK) were determined by Western blotting.
 Results: There were only few viable cells in tamoxifen- and tanshinone-treated wells, and cell viability was concentration-dependently reduced. Treatment of SNU-306 cells with tamoxifen (30 µM) or tanshinone (20 µM) alone significantly reduced the expression of Wip1 after 72 h of incubation, and the level of expression was significantly reduced in SNU-306 cells treated with combination of tamoxifen and tanshinones, relative to those treated with tamoxifen or tanshinone alone (p < 0.05). The extent of apoptosis was significantly higher in SNU-306 cells treated with tamoxifen or tanshinone alone or in combination than in control cells (p < 0.05). Expressions of Bax, caspase 3 and p53 were significantly higher in SNU-306 cells than in control cells, and were significantly higher in SNU-306 cells treated with combination of tamoxifen and tanshinone than in those treated with tamoxifen or tanshinone alone (p < 0.05). The level of expression of MAPK was significantly higher in SNU-306 cells treated with tamoxifen or tanshinone alone, and in combination treatment, than in control cells (p < 0.05).
 Conclusion: Tamoxifen and tanshinone administered alone or in combination promote apoptosis in BC cells via mechanisms involving the up-regulation and phosphorylation of MAPK.
Highlights
Breast cancer (BC) is a malignant tumor and one of the leading causes of death in women globally [1]
The present study investigated the effects of tamoxifen and tanshinone administered alone or in combination, on the proliferation of BC cells, and the underlying mechanism(s)
Results of qRT-PCR and Western blotting showed that the level of expression of wild-type p53-induced phosphatase 1 (Wip1) was significantly higher in BC cells than in HMEC cells (p < 0.05; Figure 2)
Summary
Breast cancer (BC) is a malignant tumor and one of the leading causes of death in women globally [1]. The expression of Wip is involved in the activation of various pathways [10,11,12,13] This molecule is involved in the development and metastasis of ovarian carcinoma, and its overexpression prevents the cells from undergoing apoptosis [11,12,13,14]. After 24 h of incubation, the cells were treated with varied concentrations of tamoxifen or tanshinone (10 - 50 μM) and cultured for 72 h. This was followed by the addition of 20 ml of 0.5 % MTT solution within 4 h, after which the culture medium was changed. Apoptosis in SNU-306 cells treated with tamoxifen or tanshinone (10 - 50 μM) was determined using a flow cytometer. Groups were compared using Student ttest, and values of p < 0.05 were considered statistically significant
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
