Cholesterol Metabolism: A Potential Therapeutic Target in Glioblastoma

Ahmad, Faudziah; Sun, Qian; Patel, Deven; Stommel, Jayne M.

doi:10.3390/cancers11020146

Cited by 77 publications

(75 citation statements)

References 102 publications

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“…It also serves as a precursor for steroid hormones, bile acids, vitamin D and oxysterols, and is a critical molecule for cell growth and function. [7,[12][13][14][15].…”

Section: Cholesterol Oxysterols Lxrs and Breast Cancermentioning

confidence: 99%

Cholesterol, Oxysterols and LXRs in Breast Cancer Pathophysiology

Nazih

Bard

2020

IJMS

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Breast cancer is the most frequent cancer among women. In 2018, it is estimated that 627,000 women died from breast cancer. This is approximately 15% of all cancer deaths among women (WHO 2018). Breast cancer is a multifactorial chronic disease. While important progress has been made to treat patients, many questions regarding aspects of this disease relating to carcinogenesis are still open. During carcinogenesis, cells exhibit cholesterol homeostasis deregulation. This results in an accumulation of intracellular cholesterol, which is required to sustain their high growth rate. Cholesterol efflux and influx are two metabolic pathways that are necessary to prevent cholesterol accumulation in the cells. Liver X receptors (LXRs) are nuclear receptors that, upon activation, induce the expression of ABC transporters, responsible for promoting cholesterol efflux, and the expression of IDOL (inducible degrader of low-density lipoprotein receptor), in charge of reducing cholesterol influx. Oxysterols, oxygenated derivatives of cholesterol formed through different pathways, have been discovered as LXR-specific ligands. Some oxysterols are involved in tumor formation while others are considered anti-tumor agents. In the present review, we discuss the involvement of cholesterol, oxysterols and LXRs in breast cancer pathophysiology, with an emphasis on the biological effects of LXR ligands.

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“…It also serves as a precursor for steroid hormones, bile acids, vitamin D and oxysterols, and is a critical molecule for cell growth and function. [7,[12][13][14][15].…”

Section: Cholesterol Oxysterols Lxrs and Breast Cancermentioning

confidence: 99%

Cholesterol, Oxysterols and LXRs in Breast Cancer Pathophysiology

Nazih

Bard

2020

IJMS

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“…The observed prominent antifungal profile of compounds 18a-j supports our hypothesis that new N1-substituted triazole architectures show potential as renewable antifungals. The latent antifungal activity of azoles is attributed to their ability to interfere with and disrupt fungal lanosterol biosynthesis [33], which is required for membrane permeability.…”

Section: Pharmacological Evaluationmentioning

confidence: 99%

Design, Synthesis, and Antimicrobial Evaluation of New Annelated Pyrimido[2,1-c][1,2,4]triazolo[3,4-f][1,2,4]triazines

Azab

Elkanzi

2020

Molecules

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A series of 34 new pyrimido[2,1-c] [1,2,4]triazine-3,4-diones were synthesized and fully characterized using IR, NMR, MS, and microanalytical analysis. In vitro investigation of 12 compounds of this series revealed promising antimicrobial activity of the conjugates 15a and 15f-j that were tagged with electron-withdrawing groups, with sensitivities ranging from 77% to as high as 100% of the positive control. The investigation of antimicrobial activity included Bacillus subtilis ATCC 6633, Staphylococcus aureus ATCC 6535, Pseudomonas aeruginosa ATCC 27853, and Escherichia coli ATCC 8739 (EC), and fungal strains Candida albicans ATCC 10231 and Aspergillus brasiliensis ATCC 16404.

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“…In this regard, Mtb is able to import and metabolize host cholesterol during infection, which is critical for the maintenance of Mtb infection [30]. In addition, cholesterol also is a critical carbon source during latent Mtb infection, during which Mtb is capable of using cholesterol as a carbon source [32]. Moreover, the cholesterol of macrophage host has been shown to facilitate the entry of mycobacteria into macrophages [33], where mycobacteria-activated macrophages effectively transfer the phagocytosed pathogens to the destructive microenvironment of lysosomes [34].…”

Section: Discussionmentioning

confidence: 99%

Involvement of ABC-transporters and acyltransferase 1 in intracellular cholesterol-mediated autophagy in bovine alveolar macrophages in response to the Bacillus Calmette-Guerin (BCG) infection

Zhou

Yang

et al. 2020

BMC Immunol

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Background: Understanding pathogenic mechanisms is imperative for developing novel treatment to the tuberculosis, an important public health burden worldwide. Recent studies demonstrated that host cholesterol levels have implications in the establishment of Mycobacterium tuberculosis (M. tuberculosis, Mtb) infection in host cells, in which the intracellular cholesterol-mediated ATP-binding cassette transporters (ABC-transporters) and cholesterol acyltransferase1 (ACAT1) exhibited abilities to regulate macrophage autophagy induced by Mycobacterium bovis bacillus Calmette-Guérin (BCG). Results: The results showed that a down-regulated expression of the ABC-transporters and ACAT1 in primary bovine alveolar macrophages (AMs) and murine RAW264.7 cells in response to a BCG infection. The inhibited expression of ABC-transporters and ACAT1 was associated with the reduction of intracellular free cholesterol, which in turn induced autophagy in macrophages upon to the Mycobacterial infection. These results strongly suggest an involvement of ABC-transporters and ACAT1 in intracellular cholesterol-mediated autophagy in AMs in response to BCG infection. Conclusion: This study thus provides an insight into into a mechanism by which the cholesterol metabolism regulated the autophagy in macrophages in response to mycobacterial infections.

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Cholesterol Metabolism: A Potential Therapeutic Target in Glioblastoma

Cited by 77 publications

References 102 publications

Cholesterol, Oxysterols and LXRs in Breast Cancer Pathophysiology

Cholesterol, Oxysterols and LXRs in Breast Cancer Pathophysiology

Design, Synthesis, and Antimicrobial Evaluation of New Annelated Pyrimido[2,1-c][1,2,4]triazolo[3,4-f][1,2,4]triazines

Involvement of ABC-transporters and acyltransferase 1 in intracellular cholesterol-mediated autophagy in bovine alveolar macrophages in response to the Bacillus Calmette-Guerin (BCG) infection

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