某些植物化学物质的抗氧化/抗诱变与抗增殖活性的相关性。
Correlation between Antioxidant/Antimutagenic and Antiproliferative Activity of Some Phytochemicals.
机构信息
Department of Zoology, Faculty of Science, Ain Shams University, Abbassia 11566, Cairo, Egypt.
Department of Biochemistry, Faculty of Science, Ain Shams University, Abbassia 11566, Cairo, Egypt.
出版信息
Anticancer Agents Med Chem. 2019;19(12):1481-1490. doi: 10.2174/1871520619666190528091648.
BACKGROUND
Chemotherapeutic drugs have high toxicity associated with undesirable side-effects. Now, natural products are the most important anti-cancer agents because of their low toxicity and potential effectiveness.
METHODS
The half maximal inhibitory concentration (IC50) of amygdalin, naringenin and ellagic acid against breast, colon, and liver cell lines was estimated. The antimutagenic, free radical-, superoxide radical-, and hydroxyl radical- scavenging activities of these phytochemicals were measured. The expression of p53, bid, bax, bcl2, and caspases 9, 3, and 7 was measured by quantitative real-time polymerase chain reaction (qRT-PCR) in breast and liver cells. In addition, the active Caspase 3 protein was estimated in liver cells.
RESULTS
Ellagic acid showed the highest antioxidant and antiproliferative activities. Amygdalin and naringenin with low and moderate antioxidant profiles showed a corresponding low and moderate cytotoxicity against cancer cell lines, respectively. Naringenin and ellagic acid had a significant antimutagenic activity which was detected by the Salmonella test. Ellagic acid offered a much better antimutagenic activity than naringenin. The apoptotic pathway evoked by ellagic acid in HepG2 and MCF-7 cells was investigated. The results showed that a caspase-dependent and a caspase-independent apoptosis occurred in MCF-7 and HepG2, respectively.
CONCLUSION
The antimutagenic/antioxidant properties are well correlated with the antiproliferative activity of the phytochemicals investigated. This study proved that some easy, quick and cheap assays could predict the antiproliferative activity of many nutraceuticals. Finally, this platform could help in the discovery of new anticancer agents where hundreds of compounds are investigated in the pipeline of drug discovery.
背景
化疗药物具有高毒性,伴随着不良的副作用。现在,由于其低毒性和潜在的有效性,天然产物是最重要的抗癌药物。
方法
评估了苦杏仁苷、柚皮苷和鞣花酸对乳腺癌、结肠癌和肝癌细胞系的半最大抑制浓度(IC50)。测量了这些植物化学物质的抗突变、自由基、超氧自由基和羟自由基清除活性。通过定量实时聚合酶链反应(qRT-PCR)测量乳腺癌和肝癌细胞中 p53、bid、bax、bcl2 和 caspase 9、3、7 的表达。此外,还测定了肝癌细胞中活性 Caspase 3 蛋白。
结果
鞣花酸表现出最高的抗氧化和抗增殖活性。具有低中和中等抗氧化谱的苦杏仁苷和柚皮苷对癌细胞系分别表现出相应的低中和中度细胞毒性。柚皮苷和鞣花酸具有显著的抗突变活性,这是通过沙门氏菌试验检测到的。鞣花酸的抗突变活性优于柚皮苷。研究了鞣花酸在 HepG2 和 MCF-7 细胞中诱导的凋亡途径。结果表明,caspase 依赖性和非依赖性凋亡分别发生在 MCF-7 和 HepG2 中。
结论
抗突变/抗氧化特性与所研究的植物化学物质的抗增殖活性密切相关。本研究证明了一些简单、快速和廉价的测定方法可以预测许多营养保健品的抗增殖活性。最后,该平台可以帮助发现新的抗癌药物,在药物发现的管道中可以研究数百种化合物。