Can non-cholesterol sterols indicate the presence of specific dysregulation of cholesterol metabolism in patients with colorectal cancer?

Vladimirov, Sandra; Gojković, Tamara; Zeljković, Aleksandra; Jelić‐Ivanović, Zorana; Zeljkovic, Dejan; Antonić, Tamara; Trifunović, Bratislav; Spasojević‐Kalimanovska, Vesna

doi:10.1016/j.bcp.2021.114595

Cited by 11 publications

(9 citation statements)

References 41 publications

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“…However, excess cholesterol is either exported from the cells by ATP-binding cassette transporters, or converted to cholesteryl esters with less cytotoxicity by acyl-coenzyme A:cholesterol acyltransferases and then stored in lipid droplets or secreted within lipoproteins [ 4 ]. Recent studies have revealed that dysregulation of cholesterol metabolism is not only closely associated with neurodegenerative disorders such as Alzheimer’s disease [ 5 ], Parkinson’s disease [ 6 ], Huntington’s disease [ 7 ], atherosclerosis [ 8 ], cardiovascular disease [ 9 ], and hypercholesterolemia [ 10 ], but also acts as a pathophysiological etiology of carcinogenesis in various types of cancers [ 11 , 12 , 13 ].…”

Section: Introductionmentioning

confidence: 99%

25-Hydroxycholesterol-Induced Oxiapoptophagy in L929 Mouse Fibroblast Cell Line

et al. 2021

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25-hydroxycholesterol (25-HC) is an oxysterol synthesized from cholesterol by cholesterol-25-hydroxylase during cholesterol metabolism. The aim of this study was to verify whether 25-HC induces oxiapoptophagy in fibroblasts. 25-HC not only decreased the survival of L929 cells, but also increased the number of cells with condensed chromatin and altered morphology. Fluorescence-activated cell sorting results showed that there was a dose-dependent increase in the apoptotic populations of L929 cells upon treatment with 25-HC. 25-HC-induced apoptotic cell death was mediated by the death receptor-dependent extrinsic and mitochondria-dependent intrinsic apoptosis pathway, through the cascade activation of caspases including caspase-8, -9, and -3 in L929 cells. There was an increase in the levels of reactive oxygen species and inflammatory mediators such as inducible nitric oxide synthase, cyclooxygenase-2, nitric oxide, and prostaglandin E2 in L929 cells treated with 25-HC. Moreover, 25-HC caused an increase in the expression of beclin-1 and microtubule-associated protein 1A/1B-light chain 3, an autophagy biomarker, in L929 cells. There was a significant decrease in the phosphorylation of protein kinase B (Akt) in L929 cells treated with 25-HC. Taken together, 25-HC induced oxiapoptophagy through the modulation of Akt and p53 cellular signaling pathways in L929 cells.

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Section: Introductionmentioning

confidence: 99%

25-Hydroxycholesterol-Induced Oxiapoptophagy in L929 Mouse Fibroblast Cell Line

et al. 2021

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“…However, another study reported that cholesterol homeostasis is switched to increase cholesterol biosynthesis because the relative abundance of noncholesterol sterols (NCS), as cholesterol synthesis and absorption biomarkers, was amplified in HDL particles. These data indicate cholesterol precursors are overproduced in peripheral tissues (77). Molecular mechanisms have been proposed to explain the association between cholesterol metabolism and CRC, including fluctuations in the inflammatory responses and cytokine levels that affect the proliferation and apoptosis of CRC tumor cells, as well as a reduction in oxidative stress through the reduction of oxidized LDL (oLDL) (78,79).…”

Section: Cholesterol Levels and Colorectal Cancermentioning

confidence: 99%

Cholesterol in colorectal cancer: an essential but tumorigenic precursor?

He,

Lan,

Jin

et al. 2023

Front. Oncol.

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Colorectal cancer (CRC) is one of the most lethal human malignancies, and with the growth of societies and lifestyle changes, the rate of people suffering from it increases yearly. Important factors such as genetics, family history, nutrition, lifestyle, smoking, and alcohol can play a significant role in increasing susceptibility to this cancer. On the other hand, the metabolism of several macromolecules is also involved in the fate of tumors and immune cells. The evidence discloses that cholesterol and its metabolism can play a role in the pathogenesis of several cancers because there appears to be an association between cholesterol levels and CRC, and cholesterol-lowering drugs may reduce the risk. Furthermore, changes or mutations of some involved genes in cholesterol metabolism, such as CYP7A1 as well as signaling pathways, such as mitogen-activated protein kinase (MAPK), can play a role in CRC pathogenesis. This review summarized and discussed the role of cholesterol in the pathogenesis of CRC as well as available cholesterol-related therapeutic approaches in CRC.

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“…Recent evidence from Vladimirov et al. demonstrated that colorectal cancer patients had significantly increased values of cholesterol serum precursors compared to healthy donors, suggesting that cholesterol metabolism is altered in cancer ( 280 ). This evidence allows us to speculate that such patients might present altered myelopoiesis and thus increased numbers of MDSCs and other immunoregulatory cell populations; however, intensive research using in vitro and in vivo models in distinct types of cancer is needed to confirm this hypothesis.…”

Section: Paraneoplastic Syndromesmentioning

confidence: 99%

The systemic-level repercussions of cancer-associated inflammation mediators produced in the tumor microenvironment

et al. 2022

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The tumor microenvironment is a dynamic, complex, and redundant network of interactions between tumor, immune, and stromal cells. In this intricate environment, cells communicate through membrane–membrane, ligand–receptor, exosome, soluble factors, and transporter interactions that govern cell fate. These interactions activate the diverse and superfluous signaling pathways involved in tumor promotion and progression and induce subtle changes in the functional activity of infiltrating immune cells.The immune response participates as a selective pressure in tumor development. In the early stages of tumor development, the immune response exerts anti-tumor activity, whereas during the advanced stages, the tumor establishes mechanisms to evade the immune response, eliciting a chronic inflammation process that shows a pro-tumor effect.The deregulated inflammatory state, in addition to acting locally, also triggers systemic inflammation that has repercussions in various organs and tissues that are distant from the tumor site, causing the emergence of various symptoms designated as paraneoplastic syndromes, which compromise the response to treatment, quality of life, and survival of cancer patients. Considering the tumor–host relationship as an integral and dynamic biological system, the chronic inflammation generated by the tumor is a communication mechanism among tissues and organs that is primarily orchestrated through different signals, such as cytokines, chemokines, growth factors, and exosomes, to provide the tumor with energetic components that allow it to continue proliferating. In this review, we aim to provide a succinct overview of the involvement of cancer-related inflammation at the local and systemic level throughout tumor development and the emergence of some paraneoplastic syndromes and their main clinical manifestations. In addition, the involvement of these signals throughout tumor development will be discussed based on the physiological/biological activities of innate and adaptive immune cells. These cellular interactions require a metabolic reprogramming program for the full activation of the various cells; thus, these requirements and the by-products released into the microenvironment will be considered. In addition, the systemic impact of cancer-related proinflammatory cytokines on the liver—as a critical organ that produces the leading inflammatory markers described to date—will be summarized. Finally, the contribution of cancer-related inflammation to the development of two paraneoplastic syndromes, myelopoiesis and cachexia, will be discussed.

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Can non-cholesterol sterols indicate the presence of specific dysregulation of cholesterol metabolism in patients with colorectal cancer?

Cited by 11 publications

References 41 publications

25-Hydroxycholesterol-Induced Oxiapoptophagy in L929 Mouse Fibroblast Cell Line

25-Hydroxycholesterol-Induced Oxiapoptophagy in L929 Mouse Fibroblast Cell Line

Cholesterol in colorectal cancer: an essential but tumorigenic precursor?

The systemic-level repercussions of cancer-associated inflammation mediators produced in the tumor microenvironment

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