Laboratory of Foodomics, Institute of Food Science Research, CIAL, CSIC, Nicolás Cabrera 9, 28049 Madrid, Spain; High Pressure Laboratory, Department of Chemistry, Faculty of Science, Universidad Nacional de Colombia, Carrera 30 #45-03, Bogotá D.C. 111321, Colombia.
Laboratory of Foodomics, Institute of Food Science Research, CIAL, CSIC, Nicolás Cabrera 9, 28049 Madrid, Spain.
Food Res Int. 2020 Apr;130:108938. doi: 10.1016/j.foodres.2019.108938. Epub 2019 Dec 24.
The anti-proliferative potential of Passiflora mollissima seeds, an underexplored agri-food waste, was investigated in this work by evaluating the molecular changes induced at transcript and metabolite expression levels on HT-29 human colon cancer cells. For this purpose, a pressurized-liquid extract from P. mollissima seeds obtained under optimized conditions was used for the treatment of HT-29 cells and a multi-omics strategy applied, integrating transcriptomics and metabolomics analysis, along with viability and cell cycle assays to study the molecular mechanisms that explain the anti-proliferative activity of this fruit by-product. After treatment for 48 and 72 h, the viability of HT-29 colon cancer cells was markedly affected, whereas minor effects were observed on normal human colon fibroblast cells. The bioactive extract was shown to arrest HT-29 cells in the S and G2/M phases of the cell cycle, which might be mediated by the inactivation of the FAT10 cancer signalling pathway among other genes identified as altered in the transcriptomic analysis. In addition, cellular redox homeostasis, as well as the polyamines pathway and methionine metabolism were found to be affected as suggested from the metabolomics data. Finally, the Foodomics integration enabled the identification of genes, such as MAD2L1, involved in the polyamine and glutathione metabolism, or the inactivation of the NUPR1 transcription factor, that might be related with the alteration of the intracellular ceramide levels in response to endoplasmic reticulum stress.
本研究旨在探究西番莲种子（一种未充分开发的农业食品废物）的抗增殖潜力，为此，采用优化条件下获得的西番莲种子加压液体提取物处理 HT-29 人结肠癌细胞，评估其在转录和代谢物表达水平上引起的分子变化，并应用多组学策略，整合转录组学和代谢组学分析，以及活力和细胞周期测定，研究解释该水果副产物抗增殖活性的分子机制。经 48 和 72 h 处理后，HT-29 结肠癌细胞活力明显受到影响，而对正常人类结肠成纤维细胞影响较小。生物活性提取物显示可将 HT-29 细胞阻滞在细胞周期的 S 和 G2/M 期，这可能是通过 FAT10 癌症信号通路失活以及转录组分析中鉴定的其他改变基因介导的。此外，根据代谢组学数据，还发现细胞氧化还原稳态、多胺途径和蛋氨酸代谢受到影响。最后，通过食品组学整合，鉴定了与细胞内神经酰胺水平变化相关的基因，如 MAD2L1，其参与多胺和谷胱甘肽代谢，或 NUPR1 转录因子的失活，这可能与内质网应激反应有关。
