Brockmueller Aranka, Sameri Saba, Liskova Alena, Zhai Kevin, Varghese Elizabeth, Samuel Samson Mathews, Büsselberg Dietrich, Kubatka Peter, Shakibaei Mehdi
Musculoskeletal Research Group and Tumor Biology, Chair of Vegetative Anatomy, Institute of Anatomy, Faculty of Medicine, Ludwig-Maximilian-University Munich, Pettenkoferstrasse 11, D-80336 Munich, Germany.
Department of Molecular Medicine and Genetics, Hamadan University of Medical Sciences, 6517838678 Hamadan, Iran.
Cancers (Basel). 2021 Jan 7;13(2):188. doi: 10.3390/cancers13020188.
Tumor cells develop several metabolic reprogramming strategies, such as increased glucose uptake and utilization via aerobic glycolysis and fermentation of glucose to lactate; these lead to a low pH environment in which the cancer cells thrive and evade apoptosis. These characteristics of tumor cells are known as the Warburg effect. Adaptive metabolic alterations in cancer cells can be attributed to mutations in key metabolic enzymes and transcription factors. The features of the Warburg phenotype may serve as promising markers for the early detection and treatment of tumors. Besides, the glycolytic process of tumors is reversible and could represent a therapeutic target. So-called mono-target therapies are often unsafe and ineffective, and have a high prevalence of recurrence. Their success is hindered by the ability of tumor cells to simultaneously develop multiple chemoresistance pathways. Therefore, agents that modify several cellular targets, such as energy restriction to target tumor cells specifically, have therapeutic potential. Resveratrol, a natural active polyphenol found in grapes and red wine and used in many traditional medicines, is known for its ability to target multiple components of signaling pathways in tumors, leading to the suppression of cell proliferation, activation of apoptosis, and regression in tumor growth. Here, we describe current knowledge on the various mechanisms by which resveratrol modulates glucose metabolism, its potential as an imitator of caloric restriction, and its therapeutic capacity in tumors.
肿瘤细胞会发展出多种代谢重编程策略，比如通过有氧糖酵解增加葡萄糖摄取与利用，以及将葡萄糖发酵生成乳酸；这些会导致癌细胞赖以生存并逃避凋亡的低pH环境。肿瘤细胞的这些特性被称为瓦伯格效应。癌细胞中的适应性代谢改变可归因于关键代谢酶和转录因子的突变。瓦伯格表型的特征可能成为肿瘤早期检测与治疗的有前景的标志物。此外，肿瘤的糖酵解过程是可逆的，可能代表一个治疗靶点。所谓的单靶点疗法往往不安全且无效，复发率很高。肿瘤细胞同时发展多种化疗耐药途径的能力阻碍了这些疗法的成功。因此，能够改变多个细胞靶点的药物，比如特异性靶向肿瘤细胞的能量限制，具有治疗潜力。白藜芦醇是一种天然活性多酚，存在于葡萄和红酒中，并被用于多种传统药物，它以能够靶向肿瘤信号通路的多个组分而闻名，可导致细胞增殖受抑、凋亡激活以及肿瘤生长消退。在此，我们描述了目前关于白藜芦醇调节葡萄糖代谢的各种机制、其作为热量限制模拟物的潜力以及其在肿瘤中的治疗能力的相关知识。
