Barzegar Elmira, Fouladdel Shamileh, Movahhed Tahereh Komeili, Atashpour Shekoufeh, Ghahremani Mohammad Hossein, Ostad Seyed Nasser, Azizi Ebrahim
Molecular Research Lab, Department of Pharmacology and Toxicology, Tehran University of Medical Sciences, Tehran, Iran.
Molecular Research Lab, Department of Pharmacology and Toxicology, Tehran University of Medical Sciences, Tehran, Iran ; Department of Molecular Medicine, School of Advanced Technologies in Medicine, Tehran University of Medical Sciences, Tehran, Iran.
Iran J Basic Med Sci. 2015 Apr;18(4):334-42.
Berberine, a naturally occurring isoquinoline alkaloid, has shown antitumor properties in some in vitro systems. But the effect of berberine on breast cancer has not yet been completely studied. In this study, we evaluated anticancer properties of berberine in comparison to doxorubicin.
The antiproliferative effects of berberine and doxorubicin alone and in combination were evaluated in T47D and MCF7 cell lines using MTT cytotoxicity assay. In addition, flow cytometry analysis was performed to evaluate the cell cycle alteration and apoptosis induction in these cell lines following exposure to berberine and doxorubicin alone and in combination.
The IC50 of berberine was determined to be 25 µM after 48 hr of treatment in both cell lines but for doxorubicin it was 250 nM and 500 nM in T47D and MCF-7 cell lines, respectively. Co-treatment with berberine and doxorubicin increased cytotoxicity in T47D cells more significantly than in MCF-7 cells. Flow cytometry results demonstrated that berberine alone or in combination with doxorubicin induced G2/M arrest in the T47D cells, but G0/G1 arrest in the MCF-7 cells. Doxorubicin alone induced G2/M arrest in both cell lines. Furthermore, berberine and doxorubicin alone or in combination significantly induced apoptosis in both cell lines.
Berberine alone and in combination with doxorubicin inhibited cell proliferation, induced apoptosis and altered cell cycle distribution of breast cancer cells. Therefore, berberine showed to be a good candidate for further studies as a new anticancer drug in the treatment of human breast cancer.
小檗碱是一种天然存在的异喹啉生物碱,在一些体外系统中已显示出抗肿瘤特性。但小檗碱对乳腺癌的影响尚未得到充分研究。在本研究中,我们评估了小檗碱与阿霉素相比的抗癌特性。
使用MTT细胞毒性试验评估小檗碱和阿霉素单独及联合使用对T47D和MCF7细胞系的抗增殖作用。此外,进行流式细胞术分析以评估这些细胞系在单独及联合暴露于小檗碱和阿霉素后细胞周期的改变和凋亡诱导情况。
在两种细胞系中,处理48小时后小檗碱的IC50测定为25 μM,但阿霉素在T47D和MCF - 7细胞系中的IC50分别为250 nM和500 nM。小檗碱与阿霉素联合处理对T47D细胞的细胞毒性增加比MCF - 7细胞更显著。流式细胞术结果表明,单独使用小檗碱或与阿霉素联合使用可诱导T47D细胞发生G2/M期阻滞,但在MCF - 7细胞中诱导G0/G1期阻滞。单独使用阿霉素在两种细胞系中均诱导G2/M期阻滞。此外,单独或联合使用小檗碱和阿霉素均显著诱导两种细胞系凋亡。
单独使用小檗碱以及与阿霉素联合使用均可抑制乳腺癌细胞增殖、诱导凋亡并改变细胞周期分布。因此,小檗碱显示出作为治疗人类乳腺癌的新型抗癌药物进行进一步研究的良好潜力。