Tropical Journal of Pharmaceutical Research

Original Research Article | OPEN ACCESS

Inhibitory effects of tamoxifen and tanshinone, alone or in combination, on the proliferation of breast cancer cells via activation of p38 MAPK signalling pathway

Haiyan Chen¹, Yuntao Wang², Xiaoqing Ding¹

¹Department of Hematology, Dongfang Hospital Affiliated to Beijing University of Traditional Chinese Medicine, Beijing 100078; ²Beijing YuYuanTang Clinic of Traditional Chinese Medicine, Beijing 100021, China.

For correspondence:- Xiaoqing Ding Email: DLajuanashan@yahoo.com Tel:+861067689741

Accepted: 18 February 2019 Published: 31 March 2019

Citation: Chen H, Wang Y, Ding X. Inhibitory effects of tamoxifen and tanshinone, alone or in combination, on the proliferation of breast cancer cells via activation of p38 MAPK signalling pathway. Trop J Pharm Res 2019; 18(3):533-538 doi: 10.4314/tjpr.v18i3.13

© 2019 The authors.
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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 mitogen-activated 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.

Keywords: Breast cancer, Tamoxifen, Tanshinone, expression, Apoptosis