Cholesterol lowering: role in cancer prevention and treatment

Murai, Toshiyuki

doi:10.1515/hsz-2014-0194

Cited by 173 publications

(157 citation statements)

References 102 publications

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“…For example, Ezetimibe, an FDA-approved drug, reduced preclinical prostate tumor growth by inhibiting intestinal cholesterol absorption (55,68). While this approach targets dietary uptake, it does not modulate liver produced levels in the serum.…”

Section: Cholesterol Metabolism and Its Role In Cancermentioning

confidence: 99%

The Role of Cholesterol in Cancer

2016

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The roles played by cholesterol in cancer development and the potential of therapeutically targeting cholesterol homeostasis is a controversial area in the cancer community. Several epidemiological studies report an association between cancer and serum cholesterol levels or statin use, while others suggest that there is not one. Furthermore, the Cancer Genome Atlas (TCGA) project using next-generation sequencing has profiled the mutational status and expression levels of all the genes in diverse cancers, including those involved in cholesterol metabolism, providing correlative support for a role of the cholesterol pathway in cancer development. Finally, preclinical studies tend to more consistently support a role of cholesterol in cancer with several demonstrating that cholesterol homeostasis genes can modulate development. Due to space limitations, this review provides selected examples of the epidemiological, TCGA and preclinical data, focusing on alterations in cholesterol homeostasis and its consequent effect on patient survival. In melanoma, this focused analysis, demonstrated that enhanced expression of cholesterol synthesis genes was associated with decreased patient survival. Collectively, the studies in melanoma and other cancer types, suggested a potential role of disrupted cholesterol homeostasis in cancer development but that additional studies are needed to link population based epidemiological data, the TCGA database results and preclinical mechanistic evidence to concretely resolve this controversy.

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Section: Cholesterol Metabolism and Its Role In Cancermentioning

confidence: 99%

The Role of Cholesterol in Cancer

2016

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“…It is now generally accepted that cancer cells have elevated levels of cholesterol in lipid rafts and contain more lipid rafts than their normal cell line counterparts (26,27,29,31,44). Enhanced expression of enzymes of the cholesterol pathway has been reported in many cancer cell types (31,(45)(46)(47).…”

Section: +mentioning

confidence: 99%

Human sterol 14α-demethylase as a target for anticancer chemotherapy: towards structure-aided drug design

Hargrove

Friggeri

Wawrzak

et al. 2016

Journal of Lipid Research

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“…Consequently, the lipid metabolic pathway, which is critical for lipid homeostasis, is often dysregulated in cancer (4,5). Key regulators of the lipid metabolic pathway include SREBP1a, 2 SREBP1c, and SREBP2, which function as transcription factors to control the expression of genes involved in fatty acid and cholesterol synthesis (6).…”

mentioning

confidence: 99%

Fatostatin Inhibits Cancer Cell Proliferation by Affecting Mitotic Microtubule Spindle Assembly and Cell Division

Gholkar¹,

Cheung²,

Williams

et al. 2016

Journal of Biological Chemistry

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The sterol regulatory element-binding protein (SREBP) transcription factors have become attractive targets for pharmacological inhibition in the treatment of metabolic diseases and cancer. SREBPs are critical for the production and metabolism of lipids and cholesterol, which are essential for cellular homeostasis and cell proliferation. Fatostatin was recently discovered as a specific inhibitor of SREBP cleavage-activating protein (SCAP), which is required for SREBP activation. Fatostatin possesses antitumor properties including the inhibition of cancer cell proliferation, invasion, and migration, and it arrests cancer cells in G 2 /M phase. Although Fatostatin has been viewed as an antitumor agent due to its inhibition of SREBP and its effect on lipid metabolism, we show that Fatostatin's anticancer properties can also be attributed to its inhibition of cell division. We analyzed the effect of SREBP activity inhibitors including Fatostatin, PF-429242, and Betulin on the cell cycle and determined that only Fatostatin possessed antimitotic properties. Fatostatin inhibited tubulin polymerization, arrested cells in mitosis, activated the spindle assembly checkpoint, and triggered mitotic catastrophe and reduced cell viability. Thus Fatostatin's ability to inhibit SREBP activity and cell division could prove beneficial in treating aggressive types of cancers such as glioblastomas that have elevated lipid metabolism and fast proliferation rates and often develop resistance to current anticancer therapies.

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Cholesterol lowering: role in cancer prevention and treatment

Cited by 173 publications

References 102 publications

The Role of Cholesterol in Cancer

The Role of Cholesterol in Cancer

Human sterol 14α-demethylase as a target for anticancer chemotherapy: towards structure-aided drug design

Fatostatin Inhibits Cancer Cell Proliferation by Affecting Mitotic Microtubule Spindle Assembly and Cell Division

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