Department of Clinical and Experimental Medicine, University of Foggia, 71122, Foggia, Italy.
Department of Agricultural Sciences, Food, Natural Resources and Engineering, University of Foggia, 71122, Foggia, Italy.
BMC Complement Med Ther. 2023 Sep 8;23(1):311. doi: 10.1186/s12906-023-04134-1.
Pomegranate is known for its beneficial properties due to its high content in antioxidants and might constitute a natural option for preventing and treatment of different pathologies including cancer. Since mitochondria are involved in tumorigenesis through ROS production and modulation of oxidative metabolism, we investigated the biological effects of pomegranate on cellular redox state, proliferation and metabolism in the breast cancer cell line MDA-MB-231 (MDA).
MDA were treated for 24 h with graded concentration of filtered Pomegranate juice (PJ) and tested for metabolic Flux Analysis with XFe96 Extracellular Flux Analyzer, for proliferation using the xCELLigence System Real-Time Cell Analyzer and for intracellular ROS content by Confocal Microscopy Imaging.
Cells-treatment with freshly prepared pomegranate juice (PJ) resulted in a significant reduction of the intracellular ROS content already at the lower concentration of PJ tested. Additionally, it enhanced mitochondria respiration, and decreased glycolysis at high concentrations, inhibiting at the same time cell proliferation. As pomegranate is a seasonal fruit, assessment of optimum storage conditions preserving its bio-active properties was investigated. Our results indicated that storage conditions under controlled atmosphere for 30 days was able to enhance mitochondrial respiration at the same extent than freshly extracted PJ. Conversely, freezing procedure, though retaining the antioxidant and cell-growth inhibitory property, elicited an opposite effect on the metabolic profile as compared with fresh extract.
Overall, the results of our study, on the one hand, confirms the preventive/therapeutic potential of PJ, as well as of its post-harvested processing, for cancer management. On the other hand, it highlights the intrinsic difficulties in attaining mechanistic insights when a multiplicity of effects is elicited by a crude mixture of bio-active compounds.
石榴因其富含抗氧化剂而具有有益特性，可能是预防和治疗包括癌症在内的多种疾病的天然选择。由于线粒体通过产生 ROS 和调节氧化代谢参与肿瘤发生，我们研究了石榴对乳腺癌细胞系 MDA-MB-231（MDA）细胞内氧化还原状态、增殖和代谢的生物学影响。
MDA 用不同浓度过滤后的石榴汁（PJ）处理 24 小时，并用 XFe96 细胞外通量分析仪进行代谢通量分析，用 xCELLigence 系统实时细胞分析仪检测细胞增殖，用共聚焦显微镜成像检测细胞内 ROS 含量。
细胞用新鲜制备的石榴汁（PJ）处理，即使在测试的 PJ 较低浓度下，细胞内 ROS 含量也显著降低。此外，它增强了线粒体呼吸，降低了高浓度下的糖酵解，同时抑制了细胞增殖。由于石榴是季节性水果，因此评估了保持其生物活性特性的最佳储存条件。我们的结果表明，在控制气氛下储存 30 天能够以与新鲜提取的 PJ 相同的程度增强线粒体呼吸。相反，冷冻过程虽然保留了抗氧化和抑制细胞生长的特性，但与新鲜提取物相比，对代谢谱产生了相反的影响。
总的来说，我们的研究结果一方面证实了 PJ 及其收获后加工作为癌症管理的预防/治疗潜力。另一方面，它强调了当一种复杂的生物活性化合物混合物引起多种效应时，获得机制见解的内在困难。
