scholarly journals Mitochondrial Redox Metabolism: The Epicenter of Metabolism during Cancer Progression

Antioxidants ◽  
2021 ◽  
Vol 10 (11) ◽  
pp. 1838
Author(s):  
Feroza K. Choudhury
Keyword(s):  
Cancer Cells ◽  
Cancer Progression ◽  
Redox Homeostasis ◽  
Active Role ◽  
Redox Status ◽  
Metabolic Adaptation ◽  
Adaptation To Hypoxia ◽  
Central Component ◽  
Ros Generation ◽  
Redox Metabolism

Mitochondrial redox metabolism is the central component in the cellular metabolic landscape, where anabolic and catabolic pathways are reprogrammed to maintain optimum redox homeostasis. During different stages of cancer, the mitochondrial redox status plays an active role in navigating cancer cells’ progression and regulating metabolic adaptation according to the constraints of each stage. Mitochondrial reactive oxygen species (ROS) accumulation induces malignant transformation. Once vigorous cell proliferation renders the core of the solid tumor hypoxic, the mitochondrial electron transport chain mediates ROS signaling for bringing about cellular adaptation to hypoxia. Highly aggressive cells are selected in this process, which are capable of progressing through the enhanced oxidative stress encountered during different stages of metastasis for distant colonization. Mitochondrial oxidative metabolism is suppressed to lower ROS generation, and the overall cellular metabolism is reprogrammed to maintain the optimum NADPH level in the mitochondria required for redox homeostasis. After reaching the distant organ, the intrinsic metabolic limitations of that organ dictate the success of colonization and flexibility of the mitochondrial metabolism of cancer cells plays a pivotal role in their adaptation to the new environment.

scholarly journals The metabolic adaptation mechanism of metastatic organotropism

2021 ◽  
Vol 10 (1) ◽  
Author(s):  
Chao Wang ◽  
Daya Luo
Keyword(s):  
Cancer Cells ◽  
Cancer Cell ◽  
Cancer Progression ◽  
Cancer Metabolism ◽  
Cancer Metastasis ◽  
Tumour Microenvironment ◽  
Metabolic Adaptation ◽  
Adaptation Mechanism ◽  
Metastatic Sites ◽  
The Impact

AbstractMetastasis is a complex multistep cascade of cancer cell extravasation and invasion, in which metabolism plays an important role. Recently, a metabolic adaptation mechanism of cancer metastasis has been proposed as an emerging model of the interaction between cancer cells and the host microenvironment, revealing a deep and extensive relationship between cancer metabolism and cancer metastasis. However, research on how the host microenvironment affects cancer metabolism is mostly limited to the impact of the local tumour microenvironment at the primary site. There are few studies on how differences between the primary and secondary microenvironments promote metabolic changes during cancer progression or how secondary microenvironments affect cancer cell metastasis preference. Hence, we discuss how cancer cells adapt to and colonize in the metabolic microenvironments of different metastatic sites to establish a metastatic organotropism phenotype. The mechanism is expected to accelerate the research of cancer metabolism in the secondary microenvironment, and provides theoretical support for the generation of innovative therapeutic targets for clinical metastatic diseases.

scholarly journals Redox Homeostasis and Metabolism in Cancer: A Complex Mechanism and Potential Targeted Therapeutics

2020 ◽  
Vol 21 (9) ◽  
pp. 3100 ◽  
Author(s):  
Alia Ghoneum ◽  
Ammar Yasser Abdulfattah ◽  
Bailey Olivia Warren ◽  
Junjun Shu ◽  
Neveen Said
Keyword(s):  
Cancer Cells ◽  
Cancer Progression ◽  
Metabolic Pathways ◽  
Redox Homeostasis ◽  
Ros Production ◽  
Biological Processes ◽  
Survival Pathways ◽  
Oncogenic Mutations ◽  
And Oxidative Stress ◽  
Shed Light

Reactive Oxygen Species or “ROS” encompass several molecules derived from oxygen that can oxidize other molecules and subsequently transition rapidly between species. The key roles of ROS in biological processes are cell signaling, biosynthetic processes, and host defense. In cancer cells, increased ROS production and oxidative stress are instigated by carcinogens, oncogenic mutations, and importantly, metabolic reprograming of the rapidly proliferating cancer cells. Increased ROS production activates myriad downstream survival pathways that further cancer progression and metastasis. In this review, we highlight the relation between ROS, the metabolic programing of cancer, and stromal and immune cells with emphasis on and the transcription machinery involved in redox homeostasis, metabolic programing and malignant phenotype. We also shed light on the therapeutic targeting of metabolic pathways generating ROS as we investigate: Orlistat, Biguandes, AICAR, 2 Deoxyglucose, CPI-613, and Etomoxir.

scholarly journals Metabolic cooperation between cancer and non-cancerous stromal cells is pivotal in cancer progression

Tumor Biology ◽  
2018 ◽  
Vol 40 (2) ◽  
pp. 101042831875620 ◽  
Author(s):  
Filipa Lopes-Coelho ◽  
Sofia Gouveia-Fernandes ◽  
Jacinta Serpa
Keyword(s):  
Cancer Cells ◽  
Cancer Progression ◽  
Stromal Cells ◽  
Inflammatory Cells ◽  
Metabolic Adaptation ◽  
Metabolic Cooperation ◽  
Metabolic Remodeling ◽  
Organ Tissue ◽  
Cancerous Cells

The way cancer cells adapt to microenvironment is crucial for the success of carcinogenesis, and metabolic fitness is essential for a cancer cell to survive and proliferate in a certain organ/tissue. The metabolic remodeling in a tumor niche is endured not only by cancer cells but also by non-cancerous cells that share the same microenvironment. For this reason, tumor cells and stromal cells constitute a complex network of signal and organic compound transfer that supports cellular viability and proliferation. The intensive dual-address cooperation of all components of a tumor sustains disease progression and metastasis. Herein, we will detail the role of cancer-associated fibroblasts, cancer-associated adipocytes, and inflammatory cells, mainly monocytes/macrophages (tumor-associated macrophages), in the remodeling and metabolic adaptation of tumors.

scholarly journals Extract from the Coriolus versicolor Fungus as an Anti-Inflammatory Agent with Cytotoxic Properties against Endothelial Cells and Breast Cancer Cells

2020 ◽  
Vol 21 (23) ◽  
pp. 9063
Author(s):  
Tomasz Jędrzejewski ◽  
Justyna Sobocińska ◽  
Małgorzata Pawlikowska ◽  
Artur Dzialuk ◽  
Sylwia Wrotek
Keyword(s):  
Breast Cancer ◽  
Endothelial Cells ◽  
Cancer Cells ◽  
Cancer Progression ◽  
Breast Cancer Cells ◽  
Coriolus Versicolor ◽  
Bioactive Molecules ◽  
Ros Generation ◽  
Anti Inflammatory ◽  
Risk Of Cancer

Chronic inflammation is a well-recognised tumour-enabling component, which includes bioactive molecules from cells infiltrating the tumour microenvironment and increases the risk of cancer progression. Since long-term use of the currently available anti-inflammatory drugs used in cancer therapy causes numerous side effects, the aim of this study was to investigate the effect of an extract isolated from the Coriolus versicolor fungus (CV extract) on HUVEC endothelial cells and MCF-7 breast cancer cells in a pro-inflammatory microenvironment mimicked by lipopolysaccharide (LPS). The cells were simultaneously stimulated with the LPS and CV extract. After co-treatment, the cell viability, generation of reactive oxygen species (ROS), wound-healing assay, production of the pro-inflammatory and pro-angiogenic factors (interleukin (IL) 6, IL-8, and metalloproteinase (MMP) 9)), as well as expression of Toll-like receptor (TLR) 4 and phosphorylated IκB (p-IκB) were evaluated. The results showed that the CV extract inhibited IL-6, IL-8, and MMP-9 production by the LPS-stimulated cells. This effect was accompanied by a decrease in TLR4 and p-IκB expression. The CV extract also had anti-migratory properties and induced a cytotoxic effect on the cells that was enhanced in the presence of LPS. The observed cytotoxicity was associated with an increase in ROS generation. We conclude that the CV extract possesses cytotoxic activity against cancer cells and endothelial cells and has the ability to inhibit the expression of the pro-tumorigenic factors associated with inflammation.

scholarly journals Metabolic Escape Routes of Cancer Stem Cells and Therapeutic Opportunities

Cancers ◽  
2020 ◽  
Vol 12 (6) ◽  
pp. 1436 ◽  
Author(s):  
Alice Turdo ◽  
Gaetana Porcelli ◽  
Caterina D’Accardo ◽  
Simone Di Franco ◽  
Francesco Verona ◽  
...  
Keyword(s):  
Stem Cells ◽  
Cancer Stem Cells ◽  
Cancer Cells ◽  
Cancer Progression ◽  
Stromal Cells ◽  
Metabolic Reprogramming ◽  
Metabolic Adaptation ◽  
Therapeutic Approaches ◽  
Current Therapies ◽  
Oxidative Phenotype

Although improvement in early diagnosis and treatment ameliorated life expectancy of cancer patients, metastatic disease still lacks effective therapeutic approaches. Resistance to anticancer therapies stems from the refractoriness of a subpopulation of cancer cells—termed cancer stem cells (CSCs)—which is endowed with tumor initiation and metastasis formation potential. CSCs are heterogeneous and diverge by phenotypic, functional and metabolic perspectives. Intrinsic as well as extrinsic stimuli dictated by the tumor microenvironment (TME)have critical roles in determining cell metabolic reprogramming from glycolytic toward an oxidative phenotype and vice versa, allowing cancer cells to thrive in adverse milieus. Crosstalk between cancer cells and the surrounding microenvironment occurs through the interchange of metabolites, miRNAs and exosomes that drive cancer cells metabolic adaptation. Herein, we identify the metabolic nodes of CSCs and discuss the latest advances in targeting metabolic demands of both CSCs and stromal cells with the scope of improving current therapies and preventing cancer progression.

scholarly journals Implications of Oxidative Stress in Glioblastoma Multiforme Following Treatment with Purine Derivatives

Antioxidants ◽  
2021 ◽  
Vol 10 (6) ◽  
pp. 950
Author(s):  
Marta Orlicka-Płocka ◽  
Agnieszka Fedoruk-Wyszomirska ◽  
Dorota Gurda-Woźna ◽  
Paweł Pawelczak ◽  
Patrycja Krawczyk ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Glioblastoma Multiforme ◽  
Cancer Cells ◽  
Defense Mechanisms ◽  
3D Cell Culture ◽  
Redox Status ◽  
Ros Generation ◽  
Exogenous Agents ◽  
2D And 3D ◽  
Selection Of

Recently, small compound-based therapies have provided new insights into the treatment of glioblastoma multiforme (GBM) by inducing oxidative impairment. Kinetin riboside (KR) and newly designed derivatives (8-azaKR, 7-deazaKR) selectively affect the molecular pathways crucial for cell growth by interfering with the redox status of cancer cells. Thus, these compounds might serve as potential alternatives in the oxidative therapy of GBM. The increased basal levels of reactive oxygen species (ROS) in GBM support the survival of cancer cells and cause drug resistance. The simplest approach to induce cell death is to achieve the redox threshold and circumvent the antioxidant defense mechanisms. Consequently, cells become more sensitive to oxidative stress (OS) caused by exogenous agents. Here, we investigated the effect of KR and its derivatives on the redox status of T98G cells in 2D and 3D cell culture. The use of spheroids of T98G cells enabled the selection of one derivative—7-deazaKR—with comparable antitumor activity to KR. Both compounds induced ROS generation and genotoxic OS, resulting in lipid peroxidation and leading to apoptosis. Taken together, these results demonstrated that KR and 7-deazaKR modulate the cellular redox environment of T98G cells, and vulnerability of these cells is dependent on their antioxidant capacity.

scholarly journals Insights into the New Cancer Therapy through Redox Homeostasis and Metabolic Shifts

Cancers ◽  
2020 ◽  
Vol 12 (7) ◽  
pp. 1822 ◽  
Author(s):  
Dong-Hoon Hyun
Keyword(s):  
Oxidative Stress ◽  
Cancer Therapy ◽  
Cell Survival ◽  
Cancer Cells ◽  
Redox Homeostasis ◽  
Enzyme Activation ◽  
Ros Generation ◽  
Heme Oxygenase 1 ◽  
Quinone Oxidoreductase ◽  
Cancer Pathogenesis

Modest levels of reactive oxygen species (ROS) are necessary for intracellular signaling, cell division, and enzyme activation. These ROS are later eliminated by the body’s antioxidant defense system. High amounts of ROS cause carcinogenesis by altering the signaling pathways associated with metabolism, proliferation, metastasis, and cell survival. Cancer cells exhibit enhanced ATP production and high ROS levels, which allow them to maintain elevated proliferation through metabolic reprograming. In order to prevent further ROS generation, cancer cells rely on more glycolysis to produce ATP and on the pentose phosphate pathway to provide NADPH. Pro-oxidant therapy can induce more ROS generation beyond the physiologic thresholds in cancer cells. Alternatively, antioxidant therapy can protect normal cells by activating cell survival signaling cascades, such as the nuclear factor erythroid 2-related factor 2 (Nrf2)-Kelch-like ECH-associated protein 1 (Keap1) pathway, in response to radio- and chemotherapeutic drugs. Nrf2 is a key regulator that protects cells from oxidative stress. Under normal conditions, Nrf2 is tightly bound to Keap1 and is ubiquitinated and degraded by the proteasome. However, under oxidative stress, or when treated with Nrf2 activators, Nrf2 is liberated from the Nrf2-Keap1 complex, translocated into the nucleus, and bound to the antioxidant response element in association with other factors. This cascade results in the expression of detoxifying enzymes, including NADH-quinone oxidoreductase 1 (NQO1) and heme oxygenase 1. NQO1 and cytochrome b5 reductase can neutralize ROS in the plasma membrane and induce a high NAD+/NADH ratio, which then activates SIRT1 and mitochondrial bioenergetics. NQO1 can also stabilize the tumor suppressor p53. Given their roles in cancer pathogenesis, redox homeostasis and the metabolic shift from glycolysis to oxidative phosphorylation (through activation of Nrf2 and NQO1) seem to be good targets for cancer therapy. Therefore, Nrf2 modulation and NQO1 stimulation could be important therapeutic targets for cancer prevention and treatment.

scholarly journals Redox-Mediated Mechanism of Chemoresistance in Cancer Cells

Antioxidants ◽  
2019 ◽  
Vol 8 (10) ◽  
pp. 471 ◽  
Author(s):  
Eun-Kyung Kim ◽  
MinGyeong Jang ◽  
Min-Jeong Song ◽  
Dongwoo Kim ◽  
Yosup Kim ◽  
...  
Keyword(s):  
Endoplasmic Reticulum ◽  
Endoplasmic Reticulum Stress ◽  
Cancer Cells ◽  
Cell Cycle Progression ◽  
Redox Homeostasis ◽  
Nicotinamide Adenine Dinucleotide Phosphate ◽  
Atp Synthesis ◽  
Ros Generation ◽  
Secondary Messenger ◽  
Cellular Reactive Oxygen Species

Cellular reactive oxygen species (ROS) status is stabilized by a balance of ROS generation and elimination called redox homeostasis. ROS is increased by activation of endoplasmic reticulum stress, nicotinamide adenine dinucleotide phosphate (NADPH) oxidase family members and adenosine triphosphate (ATP) synthesis of mitochondria. Increased ROS is detoxified by superoxide dismutase, catalase, and peroxiredoxins. ROS has a role as a secondary messenger in signal transduction. Cancer cells induce fluctuations of redox homeostasis by variation of ROS regulated machinery, leading to increased tumorigenesis and chemoresistance. Redox-mediated mechanisms of chemoresistance include endoplasmic reticulum stress-mediated autophagy, increased cell cycle progression, and increased conversion to metastasis or cancer stem-like cells. This review discusses changes of the redox state in tumorigenesis and redox-mediated mechanisms involved in tolerance to chemotherapeutic drugs in cancer.

scholarly journals Metabolic Constrains Rule Metastasis Progression

Cells ◽  
2020 ◽  
Vol 9 (9) ◽  
pp. 2081
Author(s):  
Niccolo’ Roda ◽  
Valentina Gambino ◽  
Marco Giorgio
Keyword(s):  
Cancer Cells ◽  
Cancer Progression ◽  
Primary Tumor ◽  
Distant Metastases ◽  
Metabolic Reprogramming ◽  
Metabolic Adaptation ◽  
Surgical Removal ◽  
Metastatic Progression ◽  
Metastasis Formation ◽  
Primary Tumor Site

Metastasis formation accounts for the majority of tumor-associated deaths and consists of different steps, each of them being characterized by a distinctive adaptive phenotype of the cancer cells. Metabolic reprogramming represents one of the main adaptive phenotypes exploited by cancer cells during all the main steps of tumor and metastatic progression. In particular, the metabolism of cancer cells evolves profoundly through all the main phases of metastasis formation, namely the metastatic dissemination, the metastatic colonization of distant organs, the metastatic dormancy, and ultimately the outgrowth into macroscopic lesions. However, the metabolic reprogramming of metastasizing cancer cells has only recently become the subject of intense study. From a clinical point of view, the latter steps of the metastatic process are very important, because patients often undergo surgical removal of the primary tumor when cancer cells have already left the primary tumor site, even though distant metastases are not clinically detectable yet. In this scenario, to precisely elucidate if and how metabolic reprogramming drives acquisition of cancer-specific adaptive phenotypes might pave the way to new therapeutic strategies by combining chemotherapy with metabolic drugs for better cancer eradication. In this review we discuss the latest evidence that claim the importance of metabolic adaptation for cancer progression.

Sign in / Sign up

Export Citation Format

Share Document