The Role of Oxidative Stress and Its Counteractive Utility in Colorectal Cancer (CRC)

Basak, Debasish; Uddin, Mohammad Nasir; Hancock, Jake

doi:10.3390/cancers12113336

Cited by 129 publications

(92 citation statements)

References 248 publications

(243 reference statements)

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“…The most frequent DNA lesions caused by ROS are 8-oxoguanine and 5-hydroxycytosine, which mispair with adenine and thymine during DNA replication, respectively [ 63 ]. High ROS levels have been observed in different diseases, including CRC [ 64 ], and might contribute to the prevalence of the p53 hotspot mutations. In line with Knudson’s two-hit hypothesis, which states that both alleles of most tumor suppressor genes need to be inactivated for promoting tumorigenesis, over 91% of tumors show a loss of p53 in both alleles, with the second copy of p53 being inactivated by mutations, chromosomal deletion, or loss-of-heterozygosity [ 65 ].…”

Section: P53 Mutations In Colorectal Cancermentioning

confidence: 99%

The Role of p53 Signaling in Colorectal Cancer

Liebl

Hofmann

2021

Cancers

172

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The transcription factor p53 functions as a critical tumor suppressor by orchestrating a plethora of cellular responses such as DNA repair, cell cycle arrest, cellular senescence, cell death, cell differentiation, and metabolism. In unstressed cells, p53 levels are kept low due to its polyubiquitination by the E3 ubiquitin ligase MDM2. In response to various stress signals, including DNA damage and aberrant growth signals, the interaction between p53 and MDM2 is blocked and p53 becomes stabilized, allowing p53 to regulate a diverse set of cellular responses mainly through the transactivation of its target genes. The outcome of p53 activation is controlled by its dynamics, its interactions with other proteins, and post-translational modifications. Due to its involvement in several tumor-suppressing pathways, p53 function is frequently impaired in human cancers. In colorectal cancer (CRC), the TP53 gene is mutated in 43% of tumors, and the remaining tumors often have compromised p53 functioning because of alterations in the genes encoding proteins involved in p53 regulation, such as ATM (13%) or DNA-PKcs (11%). TP53 mutations in CRC are usually missense mutations that impair wild-type p53 function (loss-of-function) and that even might provide neo-morphic (gain-of-function) activities such as promoting cancer cell stemness, cell proliferation, invasion, and metastasis, thereby promoting cancer progression. Although the first compounds targeting p53 are in clinical trials, a better understanding of wild-type and mutant p53 functions will likely pave the way for novel CRC therapies.

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Section: P53 Mutations In Colorectal Cancermentioning

confidence: 99%

The Role of p53 Signaling in Colorectal Cancer

Liebl

Hofmann

2021

Cancers

172

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“…Oxidative stress resulting from increased production of reactive oxygen species (ROS) by various stimuli is also strongly associated with the development of CRC and IBD [ 154 , 155 , 156 , 157 , 158 , 159 , 160 ]. Enhanced oxidative stress induces increased DNA base oxidation (8OHdG-8hydroxy-2’-deoxyguanosine) and lipid peroxidation under conditions of inflammation and carcinogenesis in human subjects [ 161 , 162 ].…”

Section: Beneficial Effects Of Brown Algae and Fx In Humanmentioning

confidence: 99%

Fucoxanthin and Colorectal Cancer Prevention

Terasaki

Kubota

Kojima

et al. 2021

Cancers

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Colorectal cancer (CRC), which ranks among the top 10 most prevalent cancers, can obtain a good outcome with appropriate surgery and/or chemotherapy. However, the global numbers of both new cancer cases and death from CRC are expected to increase up to 2030. Diet-induced lifestyle modification is suggested to be effective in reducing the risk of human CRC; therefore, interventional studies using diets or diet-derived compounds have been conducted to explore the prevention of CRC. Fucoxanthin (Fx), a dietary carotenoid, is predominantly contained in edible brown algae, such as Undaria pinnatifida (wakame) and Himanthalia elongata (Sea spaghetti), which are consumed particularly frequently in Asian countries but also in some Western countries. Fx is responsible for a majority of the anticancer effects exerted by the lipophilic bioactive compounds in those algae. Interventional human trials have shown that Fx and brown algae mitigate certain risk factors for CRC; however, the direct mechanisms underlying the anti-CRC properties of Fx remain elusive. Fx and its deacetylated type “fucoxanthinol” (FxOH) have been reported to exert potential anticancer effects in preclinical cancer models through the suppression of many cancer-related signal pathways and the tumor microenvironment or alteration of the gut microbiota. We herein review the most recent studies on Fx as a potential candidate drug for CRC prevention.

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“…Therefore, mitoNEET governs VDAC1 permeability in a redox-sensitive way, inhibiting VDAC1 in high redox stress conditions. Oxidative stress is increased in CRC (115); thus, the interaction of mitoNEET with VDAC1 can be altered in CRC.…”

Section: Regulation Of Vdac1 By Protein-protein Interactions and Redox Stressmentioning

confidence: 99%

Energy Metabolic Plasticity of Colorectal Cancer Cells as a Determinant of Tumor Growth and Metastasis

et al. 2021

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Metabolic plasticity is the ability of the cell to adjust its metabolism to changes in environmental conditions. Increased metabolic plasticity is a defining characteristic of cancer cells, which gives them the advantage of survival and a higher proliferative capacity. Here we review some functional features of metabolic plasticity of colorectal cancer cells (CRC). Metabolic plasticity is characterized by changes in adenine nucleotide transport across the outer mitochondrial membrane. Voltage-dependent anion channel (VDAC) is the main protein involved in the transport of adenine nucleotides, and its regulation is impaired in CRC cells. Apparent affinity for ADP is a functional parameter that characterizes VDAC permeability and provides an integrated assessment of cell metabolic state. VDAC permeability can be adjusted via its interactions with other proteins, such as hexokinase and tubulin. Also, the redox conditions inside a cancer cell may alter VDAC function, resulting in enhanced metabolic plasticity. In addition, a cancer cell shows reprogrammed energy transfer circuits such as adenylate kinase (AK) and creatine kinase (CK) pathway. Knowledge of the mechanism of metabolic plasticity will improve our understanding of colorectal carcinogenesis.

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The Role of Oxidative Stress and Its Counteractive Utility in Colorectal Cancer (CRC)

Cited by 129 publications

References 248 publications

The Role of p53 Signaling in Colorectal Cancer

The Role of p53 Signaling in Colorectal Cancer

Fucoxanthin and Colorectal Cancer Prevention

Energy Metabolic Plasticity of Colorectal Cancer Cells as a Determinant of Tumor Growth and Metastasis

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