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X-Nuclei MRI and Energy Metabolism
Published in Guillaume Madelin, X-Nuclei Magnetic Resonance Imaging, 2022
Warburg effect: Aerobic glycolysis in cancer cells. Warburg et al. [18, 19] discovered in the 1920s that cancer cells have a common altered metabolism that includes increased glucose uptake and fermentation of glucose to lactate as a preferred ATP production pathway instead of cellular respiration, even in presence of oxygen. This pathway is also often called aerobic glycolysis, and this phenomenon is thus called the Warburg effect. This discovery let Warburg to propose what is now called the Warburg hypothesis, which postulates that tumorigenesis is mainly a consequence of an insufficient cellular respiration caused by mitochondrial dysfunction [20]. It as however later been shown in more recent studies that mitochondria in some type of cancer cells are actually still fully functional, and that the Warburg effect is thus not consistent across all cancer types [21].
Hypoxia-Responsive Nanomedicines
Published in Lin Zhu, Stimuli-Responsive Nanomedicine, 2021
Federico Perchea, Kanjiro Miyata
Since hypoxia reduces ATP production by oxidative phosphorylation in the mitochondria, hypoxic tumor cells use anaerobic glycolysis as energy source [52]. HIF-1a regulates glycolysis at several steps from increased glucose endocytosis (upregulation of glucose transporter 1, GLUT1), glucose degradation (pyruvate dehydrogenase kinase, PDHK), to exocytosis of the by-product lactate (monocarboxylate transporter 4, MCT-4) [53, 54]. In addition to direct ATP generation, glycolysis further supports cancer progression as intermediate products are shared with synthesis pathways of lipids, proteins, and nucleic acids [52, 55]. Contribution of glycolysis to nucleotide synthesis is so important to support cancer cell proliferation that enhanced glycolysis is also evident in oxygenated tumor tissues, a phenomenon called aerobic glycolysis, the Warburg effect [52].
Mammalian Cell Physiology
Published in Anthony S. Lubiniecki, Large-Scale Mammalian Cell Culture Technology, 2018
In general, cells that are rapidly growing or have the capacity to grow rapidly also tend to rapidly remove glucose from the culture medium (55, 56, 58, 70, 73, 74, 76, 146, 151). Much of the glucose in these cells is converted to lactic acid in the presence of sufficient oxygen, which is generally referred to as aerobic glycolysis. A notable example of elevated aerobic glycolysis was demonstrated by Brand (56) and by Brand et al. (55) in resting and mitogenically stimulated thymocytes. They found that thymocytes stimulated with concanavalin A and/or interleukin 2 increased their metabolism of glucose 53-fold. The stimulated (proliferating) thymocytes converted 90% of the metabolized glucose to lactate whereas resting thymocytes converted only 53%. This is an example of a normal cell population altering its metabolism and growth rate in response to mitogenic stimulation.
Malignant growth of arsenic-transformed cells depends on activated Akt induced by reactive oxygen species
Published in International Journal of Environmental Health Research, 2023
Qun Lou, Fuxun Chen, Bingyang Li, Meichen Zhang, Fanshuo Yin, Xiaona Liu, Zaihong Zhang, Xin Zhang, Chenlu Fan, Yanhui Gao, Yanmei Yang
Two hallmarks of rapid proliferation cells and tumor cells that enable cell growth are cells growth-and-division cycle acceleration(Hanahan and Weinberg 2000) and reprogramming of energy metabolism(Pavlova and Thompson 2016). Uncontrolled cell proliferation has been recognized to be a major event in carcinogens(Tomatis 1993) and that always generated by alterations in the regulation of the core cell cycle machinery. Cyclin D1, a crucial sensor and integrator of extracellular signals, is one of the more frequently altered cell cycle regulators in cancers and it can be activated by growth factors and stress(Kim and Diehl 2009). Actually, overexpression of Cyclin D1 induced by carcinogens has been considered to be the contributor to proliferation of transformed cell(Ding et al. 2009; Alteri et al. 2013). We selected three passages to eight passages L-02-As cells and parent L-02 cells for follow-up researches in this study. Transformed L-02-As cells, like other arsenic-transformed cells, represent a substantial increase in cell proliferation as compared with control L-02 cells. Furthermore, the expression of Cyclin D1 was enhanced in the transformed L-02-As cells. This finding promoted the view that cells cycle progression was accelerated in malignant transformed L-02-As cells. It always exhibits a trait with increased aerobic glycolysis in rapidly or malignant proliferation cells, in addition to changing cell cycle progression. Through metabolic reprogramming, malignant proliferation cells and tumor cells constitute an early and rapid adaptation upon hypoxia, oncogenic gain-of-function and loss-of function of suppressor genes in order to meet biosynthetic and bioenergetic demands in growing tumors and malignant progression(Vaupel et al. 2019). L-02-As cells have a stronger aerobic glycolysis capacity and overexpression of HK2 in our study. Over all, arsenic-induced malignant-transformed L-02-As cells also have characteristics similar characteristics to tumor cells, such as rapid cell cycle progression and increased aerobic glycolysis.