Kapadia Govind J, Rao G Subba, Ramachandran Cheppail, Iida Akira, Suzuki Nobutaka, Tokuda Harukuni
College of Pharmacy, Howard University, 2300 4th St. NW, Washington, DC 20059, USA.
J Complement Integr Med. 2013 Jun 26;10:/j/jcim.2013.10.issue-1/jcim-2013-0007/jcim-2013-0007.xml. doi: 10.1515/jcim-2013-0007.
Although a wide variety of cytotoxic plant extracts and phytochemicals are known to act synergistically with anticancer drug doxorubicin (D), their clinical application is hindered by safety concerns of such combination therapy. Our earlier studies showed that red beetroot (Beta vulgaris L.) extract (B), approved by Food and Drug Administration and European Union as red food color E162, reduced multi-organ tumor formations in various animal models when administered in drinking water. This led us to postulate that a long-term daily exposure to low doses of B through diet might be safe and sufficient to produce cancer chemopreventive effect in humans. Further, our recent comparative cytotoxic investigation with B and D in several human cancer cell lines indicated their potential for synergistic activity. Since B is considered safe for human use with no known toxicity, we conducted the present study to evaluate its synergistic antiproliferative activity with D against pancreatic (PaCa), breast (MCF-7) and prostate (PC-3) tumor cells of human origin. Different concentrations of B and D (0.29-290 μg/ml) and in various combinations (B:D ratio = 1:0, 1:1, 5:1, 1:5 and 0:1) were tested for cytotoxic effects against the three cancer cells. The viability of cells was assessed after 72 h incubation with various combinations of B and D using the trypan-blue staining method. The cytotoxic data were analyzed by the combination index method of Chou and Talalay to establish synergy between B and D. The results indicated that an overall positive reduction in drug concentration was achieved by D when combined with B in its cytotoxicity profile in the three human cancer cells tested. The synergistic cytotoxicity was best when the B:D ratio of 1:5 was used in PaCa cells at IC50, IC75 and IC90 dose levels and in MCF-7 cells at IC90 dose level. These results warrant further studies on the potential of red beetroot extract-doxorubicin combination in treating human cancers.
尽管已知多种细胞毒性植物提取物和植物化学物质可与抗癌药物阿霉素（D）协同作用，但其联合疗法的临床应用因安全性问题而受到阻碍。我们早期的研究表明，红甜菜根（Beta vulgaris L.）提取物（B），经美国食品药品监督管理局和欧盟批准作为红色食用色素E162，当通过饮用水给药时，可减少各种动物模型中的多器官肿瘤形成。这使我们推测，通过饮食长期每日接触低剂量的B可能是安全且足以在人体中产生癌症化学预防作用的。此外，我们最近在几种人类癌细胞系中对B和D进行的比较细胞毒性研究表明它们具有协同活性的潜力。由于B被认为对人类使用安全且无已知毒性，我们进行了本研究以评估其与D对人源胰腺（PaCa）、乳腺（MCF - 7）和前列腺（PC - 3）肿瘤细胞的协同抗增殖活性。测试了不同浓度的B和D（0.29 - 290μg/ml）以及各种组合（B:D比例 = 1:0、1:1、5:1、1:5和0:1）对三种癌细胞的细胞毒性作用。使用台盼蓝染色法在与B和D的各种组合孵育72小时后评估细胞活力。通过Chou和Talalay的联合指数法分析细胞毒性数据以确定B和D之间的协同作用。结果表明，在测试的三种人类癌细胞中，D与B联合时，其细胞毒性谱中药物浓度总体呈正向降低。当在IC50、IC75和IC90剂量水平的PaCa细胞以及IC90剂量水平的MCF - 7细胞中使用1:5的B:D比例时，协同细胞毒性最佳。这些结果为进一步研究红甜菜根提取物 - 阿霉素联合治疗人类癌症的潜力提供了依据。
