7-Ketocholesterol overcomes drug resistance in chronic myeloid leukemia cell lines beyond MDR1 mechanism

Rosa-Fernandes, Lívia; Stern, Ana Carolina Bassi; Cavaglieri, Rita de Cássia; Nogueira, Fábio César Sousa; Domont, Gilberto B.; Palmisano, Giuseppe; Bydlowski, Sérgio Paulo

doi:10.1016/j.jprot.2016.06.011

Cited by 24 publications

(23 citation statements)

References 62 publications

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“…7-Ketocholesterol was recently suggested as a potential diagnostic and predictive biomarker of Niemann-Pick disease (Boenzi 2016). It was also shown to be a cytotoxic and sensitizing agent in multidrug resistant chronic myeloid leukemia cell lines in vitro (Rosa Fernandes 2017), but there is no report about its role in human cancer onset or progression in vivo .…”

Section: Discussionmentioning

confidence: 99%

Selective changes in cholesterol metabolite levels in plasma of breast cancer patients after tumor removal

Souček

Vrána

Ueng

et al. 2017

Clinical Chemistry and Laboratory Medicine (CCLM)

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Introduction Oxygenated metabolites of cholesterol (“oxysterols”) can influence carcinogenesis and contribute to resistance to endocrine therapy, an effect mostly described in vitro. Objectives We sought to establish a method for screening plasma levels of oxysterols in breast cancer patients, estimate their individual variability and detection limits, and provide basic information about their roles in tumor biology. Method Liquid-chromatography coupled with tandem mass spectrometry was used for determination of levels of 25-hydroxycholesterol, 27-hydroxycholesterol, 7α-hydroxycholesterol, and 7-ketocholesterol in plasma sample pairs from patients before and 12–24 months after surgical removal of tumors (n=24). Deuterated standards of all oxysterols were used for method validation. Result All oxysterols were successfully detected in patient plasma samples. A significant increase in the level of 7-ketocholesterol was observed in the samples following tumor removal and the start of therapy compared to the sampling before (p=0.002). This increase was unrelated to personal characteristics of patients, expression of estrogen receptor, or to adjuvant therapy type. Conclusion This study shows, for the first time, that circulating levels of oxysterols, especially 7-ketocholesterol, may reflect the presence of tumor cells in patients.

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Section: Discussionmentioning

confidence: 99%

Selective changes in cholesterol metabolite levels in plasma of breast cancer patients after tumor removal

Souček

Vrána

Ueng

et al. 2017

Clinical Chemistry and Laboratory Medicine (CCLM)

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“…The immortalized strains constitute a simple and representative model system for functional studies and therapeutic targets. As each cell line may have unique characteristics, specific studies should take these characteristics into account [37].…”

Section: Stem Cell Culture Methodsmentioning

confidence: 99%

Traditional and Advanced Cell Cultures in Hematopoietic Stem Cell Studies

Ribeiro-Filho

Levy

Ruiz

et al. 2019

Cells

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Hematopoiesis is the main function of bone marrow. Human hematopoietic stem and progenitor cells reside in the bone marrow microenvironment, making it a hotspot for the development of hematopoietic diseases. Numerous alterations that correspond to disease progression have been identified in the bone marrow stem cell niche. Complex interactions between the bone marrow microenvironment and hematopoietic stem cells determine the balance between the proliferation, differentiation and homeostasis of the stem cell compartment. Changes in this tightly regulated network can provoke malignant transformation. However, our understanding of human hematopoiesis and the associated niche biology remains limited due to accessibility to human material and the limits of in vitro culture models. Traditional culture systems for human hematopoietic studies lack microenvironment niches, spatial marrow gradients, and dense cellularity, rendering them incapable of effectively translating marrow physiology ex vivo. This review will discuss the importance of 2D and 3D culture as a physiologically relevant system for understanding normal and abnormal hematopoiesis.

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“…The pro-apoptotic or cytostatic activity of oxysterols observed in various model cancer cell lines, e.g., murine lymphoma [73], human lymphoma and leukemic cells [74–76], as well as in non-tumor cells, e.g., thymocytes [73], retina-derived cells [77], adipose tissue-derived mesenchymal stem cells [78] and rat and human vascular smooth muscle cells [15, 16], suggests that these effects have universal importance.…”

Section: Other Malignanciesmentioning

confidence: 99%

The Role of Oxysterols in Human Cancer

Kloudová

Guengerich

Souček

2017

Trends in Endocrinology & Metabolism

147

115

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Oxysterols are oxygenated derivatives of cholesterol formed in the human body or ingested in the diet. By modulating the activity of many proteins, e.g., liver X receptors, oxysterol-binding proteins, or some ATP binding cassette transporters, oxysterols can affect many cellular functions and influence various physiological processes, e.g., cholesterol metabolism, membrane fluidity regulation, intracellular signaling pathways. Therefore, the role of oxysterols is also important in pathological conditions, e.g., atherosclerosis, diabetes mellitus type 2, neurodegenerative disorders. Finally, current evidence suggests that oxysterols play a role in malignancies, such as breast, prostate, colon, and bile duct cancer. This review summarizes the physiological importance of oxysterols in the human body, with a special emphasis on their roles in various tumors.

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7-Ketocholesterol overcomes drug resistance in chronic myeloid leukemia cell lines beyond MDR1 mechanism

Cited by 24 publications

References 62 publications

Selective changes in cholesterol metabolite levels in plasma of breast cancer patients after tumor removal

Selective changes in cholesterol metabolite levels in plasma of breast cancer patients after tumor removal

Traditional and Advanced Cell Cultures in Hematopoietic Stem Cell Studies

The Role of Oxysterols in Human Cancer

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