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Targeted Therapy for Cancer Stem Cells
Published in Surinder K. Batra, Moorthy P. Ponnusamy, Gene Regulation and Therapeutics for Cancer, 2021
Rama Krishna Nimmakayala, Saswati Karmakar, Garima Kaushik, Sanchita Rauth, Srikanth Barkeer, Saravanakumar Marimuthu, Moorthy P. Ponnusamy
Cancer cells undergo an extensive metabolic adaptation, which is one of their significant features. Glycolysis, which converts glucose into pyruvate through a series of steps, produces two ATP molecules per one glucose molecule. In the presence of oxygen, cells use oxidative phosphorylation, which produces 36 molecules of ATP per molecule of glucose. Majority of the studies suggest that cancer cells undergo Warburg effect, where cancer cells depend on glycolysis even in the presence of oxygen and convert pyruvate to lactate. If sufficient levels of glucose are available, glycolysis can produce ATPs more rapidly as compared to oxidative phosphorylation.
Mitochondrial Dysfunction in Chronic Disease
Published in Peter M. Tiidus, Rebecca E. K. MacPherson, Paul J. LeBlanc, Andrea R. Josse, The Routledge Handbook on Biochemistry of Exercise, 2020
Christopher Newell, Heather Leduc-Pessah, Aneal Khan, Jane Shearer
Hexokinase is an enzyme responsible for glycolysis initiation. As an anti-apoptotic mediator, VDAC1 enables hexokinase to bind to the OMM and access ATP for the generation of a concentration gradient that drives glycolysis (15). This mechanism is up-regulated in many malignant cancer cell lines, thus enabling sustained cell growth—the basis of the Warburg effect. Under conditions facilitating apoptosis, VDAC1 is hypothesized to interact with the monomeric cytosolic protein BAX and the OMM localized protein BAK (141). The BH3:groove model suggests that upstream regulation by BH3 and Bcl-2 proteins initiates a signalling cascade, which enables BAX to migrate to the OMM (141). Following migration of BAX to the OMM, BAX or BAK are able to self- or hetero-oligomerize, which results in mitochondrial permeabilization through formation of large oligomeric pore complexes (28). Interestingly, it is also proposed that the same protein grooves responsible for BAX and BAK apoptotic signalling may also be the site of pro-survival proteins which inhibit the oligomerization process from occurring (28). The formation of these mitochondrial pores enables cytochrome c to be released into the cytosol as a pro-apoptotic signalling molecule. Once released, cytochrome c cleaves and activates caspase 9, which perpetuates the apoptosis cascade and results in cell death (55).
Mitochondrial Dysfunction in Breast Cancer
Published in Shamim I. Ahmad, Handbook of Mitochondrial Dysfunction, 2019
Thalita Basso Scandolara, Letícia Madureira Pacholak, Thayse Fachin Cormanique, Rodrigo Kern, Carolina Panis
Mitochondrial dysfunction is implicated in cancer induction, by altering cell responsiveness to apoptotic signals and modifying its capability to deal with the energetic metabolism (Ksiȩzakowska-Łakoma, Zyła, and Wilczyński 2014). This event is a hallmark of cancer, and in association with sustained chronic inflammation and oxidative stress generation, contributes to fuel the cellular growth and proliferation (Samadi et al. 2015). Mitochondrial reprogramming energy metabolism emerged as a new hallmark of cancer few years ago, although its basis have had described decades ago (Hanahan and Weinberg 2011). Named as “Warburg effect” [reporting to Otto Warburg, more than 50 years ago first described this metabolic switch in cancer cells Warburg 1931, 1956a, 1956b]; this phenomenon occurs in cancer cells that, in spite of with oxygen availability, prefer the aerobic glycolysis route for getting energy.
Toxicity of Persian Gulf shell-less marine mollusc (Peronia peronii) methanolic extract on melanoma tumor mitochondria
Published in Cutaneous and Ocular Toxicology, 2023
Yalda Arast, Aida Jabbarzadeh, Farahnaz Tanbakosazan, Abdollah Arjmand, Amir. Vazirizadeh, Jalal Pourahmad
Numerous studies have shown that it is essential to use natural phytochemicals and plant or marine animal extracts and stop the metastatic and angiogenic cycle, which is one of the main stages in cancer progression, to reduce the morbidity and mortality of cancer as well as prevent chemotherapy [10]. In the treatment of cancer by marine animals, cell cycle interruption is used, which causes apoptosis. This type of treatment uses a variety of pathways such as ROS. To maintain homeostasis in the body, apoptosis is a physiological and biological process, which in case of disorder can lead to pathological conditions and diseases [11,13]. The Warburg effect is caused by a lack of respiration and ATP synthesis because of mitochondrial malfunction. According to recent findings, one of the most critical issues is that the numerous cancerous cells with appropriate mitochondrial respiration have increased glycolytic activities. Compared to non-cancerous tissues, including fibroblasts or melanocytes, multiple investigations have shown that melanoma cells have more significant activities of OXPHOS and glycolysis [14,15]. To combat Melanoma, finding new anti-tumor components that trigger apoptosis is essential.
Effects of Fasting on Chemotherapy Treatment Response: A Systematic Review of Current Evidence and Suggestions for the Design of Future Clinical Trials
Published in Nutrition and Cancer, 2022
Esther Heyde Selke Costa, Jenifer Faria Krüger, Carolina Q. Camargo, Vinícius Basso Preti, Elaine Hillesheim, Estela I. Rabito
Although fasting may result in slow tumor growth, none of the studies evaluated treatment efficacy. Cancer cells exhibit an elevated rate of glycolysis known as the “Warburg effect” (WE), consequently these cells rely on a higher rate of glucose uptake. Fasting can promote reduced glucose availability and result in a switch from aerobic glycolysis (WE) to mitochondrial oxidative phosphorylation in cancer cells, which will sustain cancer cell growth in a nutrient deprived setting. However, this switch increases Reactive Oxygen Species (ROS) production as a result of increased mitochondrial respiratory activity and a possible reduction in cellular redox potential (3, 8). In addition, direct or indirect generation of ROS is one of the most common mechanisms of action of chemotherapy drugs. ROS are a mediator of apoptosis, intracellular accumulation of these species can cause a loss of mitochondrial membrane potential, release of citochrome C with subsequent activation of caspases resulting in apoptosis (17, 18). Increased ROS production and reduced antioxidant protection because of the switch from the WE, leading to oxidative stress in cancer cells, can possibly enhance even more the activity of chemotherapeutics (3, 7). ROS generation can also be accounted for the incidence of adverse events related to treatment (19), but cancer cells are likely more prone to oxidative stress induced apoptosis than normal cells (18).
Anticancer nanomedicines harnessing tumor microenvironmental components
Published in Expert Opinion on Drug Delivery, 2022
Yinggang Li, Zhonglan Chen, Lei Gu, Zhengyu Duan, Dayi Pan, Zhuping Xu, Qiyong Gong, Youping Li, Hongyan Zhu, Kui Luo
In addition to cellular components and the ECM, there are many other extracellular chemical/biological in the TME, such as a low pH, hypoxia, a high redox potential, and a high concentration of reactive oxygen species (ROS) and a number of excessive enzymes. These unique physiological characteristics in the TME are highly correlated with abnormal tumor growth and metabolic reprogramming during the development of tumor tissues [30,44]. Normal cells produce energy from aerobic glycolysis, while cancer cells often use oxygen-independent glycolysis to generate excess energy for their abnormal growth after they adapt to an oxygen-starving environment within the tumor [45]. This change in the tumor metabolism is called the Warburg effect. Through this abnormal metabolism, tumor cells produce a large amount of lactic acid, excess protons, and carbon dioxide, resulting in acidification of the extracellular TME and a pH between 6.5 and 6.8 in a tumor site [46].