Berberine Shows Proapoptotic Effect and Potentiation of Cytotoxic Drugs Acitivity in Colorectal Adenocarcinoma Cells

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Abstract

Colorectal cancer, despite advances in treatment and diagnosis, is one of the most common causes of death from cancer. Conventional anticancer treatment is associated with serious side effects, therefore, new strategies are needed to reduce its toxicity. Natural compound berberine has shown antiproliferative activity against various cancer cells including colon. To investigate antiproliferative effect of berberine in human colorectal adenocarcinoma cells and its ability to potentiate the effect of convenient cytostatics taxol, docetaxel, doxorubicin and cisplatin we used MTT assay and flow cytometry was used to detect its proapoptotic effect and effect on cell cycle. In our experiments we observed significant antiproliferative activity of berberine chloride with IC50= 6.7526 μM. Combination of berberine chloride (1μM) with taxol, docetaxel, doxorubicin and carboplatin significantly increased their antiproliferative activity and decreased their IC50 values. Cell cycle analysis revealed increase in sub-G0 /G1 fraction considered as apoptotic and very mild increase in G0/G1 fraction in berberine chloride (5μM) treated cells. proapoptotic effect of berberine chloride (5μM) was confirmed by Annexin V/PI staining. Based on our results, we can assume that berberine has antiproliferative effect and the combination of berberine with cytostatics could be a promising alternative treatment for cancer. Further studies are necesary to investigate the exact mechanisms of action and drug – drug interactions.
小檗碱对结直肠癌细胞的促凋亡作用及细胞毒性药物活性的增强作用
尽管在治疗和诊断方面取得了进展,但结直肠癌仍是最常见的癌症死亡原因之一。传统的抗癌治疗具有严重的副作用,因此需要新的策略来降低其毒性。天然化合物小檗碱对包括结肠癌在内的多种癌细胞具有抗增殖活性。为了研究小檗碱对人结直肠癌腺癌细胞的抗增殖作用及其增强紫杉醇、多西紫杉醇、阿霉素和顺铂等常用细胞抑制剂作用的能力,我们采用MTT法和流式细胞术检测其促凋亡作用和对细胞周期的影响。实验结果表明,氯化小檗碱具有显著的抗增殖活性,IC50= 6.7526 μM。盐酸小檗碱(1μM)与紫杉醇、多西紫杉醇、阿霉素和卡铂联合使用可显著提高其抗增殖活性,降低其IC50值。细胞周期分析显示,在氯化小檗碱(5μM)处理的细胞中,被认为是凋亡的亚G0/G1部分增加,G0/G1部分有非常轻微的增加。Annexin V/PI染色证实氯化小檗碱(5μM)的促凋亡作用。根据我们的研究结果,我们可以假设小檗碱具有抗增殖作用,小檗碱与细胞抑制剂的结合可能是一种有希望的癌症替代治疗方法。需要进一步研究其确切的作用机制和药物-药物相互作用。
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