Alimohammadi Mohammad, Lahiani Mohamed Hassen, McGehee Diamond, Khodakovskaya Mariya
Department of Biology, University of Arkansas at Little Rock, Little Rock, Arkansas, United States of America.
Institute of Biology and Soil Sciences, Far-Eastern Branch of Russian Academy of Sciences, Vladivostok, Russia.
PLoS One. 2017 Apr 27;12(4):e0175778. doi: 10.1371/journal.pone.0175778. eCollection 2017.
In recent years, by extensive achievements in understanding the mechanisms and the pathways affected by cancer, the focus of cancer research is shifting from developing new chemotherapy methods to using natural compounds with therapeutic properties to reduce the adverse effects of synthetic drugs on human health. We used fruit extracts from previously generated human type I InsP 5-ptase gene expressing transgenic tomato plants for assessment of the anti-cancer activity of established genetically modified tomato lines. Cellular assays (MTT, Fluorescent microscopy, Flow Cytometry analysis) were used to confirm that InsP 5-ptase fruit extract was more effective for reducing the proliferation of breast cancer cells compared to wild-type tomato fruit extract. Metabolome analysis of InsP 5-ptase expressing tomato fruits performed by LC-MS identified tomato metabolites that may play a key role in the increased anti-cancer activity observed for the transgenic fruits. Total transcriptome analysis of cancer cells (MCF-7 line) exposed to an extract of transgenic fruits revealed a number of differently regulated genes in the cells treated with transgenic extract compared to untreated cells or cells treated with wild-type tomato extract. Together, this data demonstrate the potential role of the plant derived metabolites in suppressing cell viability of cancer cells and further prove the potential application of plant genetic engineering in the cancer research and drug discovery.
近年来，随着在理解癌症影响机制和途径方面取得的广泛成果，癌症研究的重点正从开发新的化疗方法转向使用具有治疗特性的天然化合物，以减少合成药物对人类健康的不利影响。我们使用先前生成的表达人I型肌醇五磷酸酶基因的转基因番茄植株的果实提取物，来评估已建立的转基因番茄品系的抗癌活性。细胞实验（MTT法、荧光显微镜观察、流式细胞术分析）用于证实，与野生型番茄果实提取物相比，肌醇五磷酸酶果实提取物在抑制乳腺癌细胞增殖方面更有效。通过液相色谱 - 质谱联用对表达肌醇五磷酸酶的番茄果实进行代谢组分析，确定了一些番茄代谢物，它们可能在转基因果实观察到的抗癌活性增强中起关键作用。对暴露于转基因果实提取物的癌细胞（MCF - 7细胞系）进行的全转录组分析显示，与未处理细胞或用野生型番茄提取物处理的细胞相比，用转基因提取物处理的细胞中有许多基因的表达受到不同调控。总之，这些数据证明了植物源代谢物在抑制癌细胞活力方面的潜在作用，并进一步证明了植物基因工程在癌症研究和药物发现中的潜在应用。
