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      The role of cholesterol metabolism and cholesterol transport in carcinogenesis: a review of scientific findings, relevant to future cancer therapeutics

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          Abstract

          While the unique metabolic activities of malignant tissues as potential targets for cancer therapeutics has been the subject of several recent reviews, the role of cholesterol metabolism in this context is yet to be fully explored. Cholesterol is an essential component of mammalian cell membranes as well as a precursor of bile acids and steroid hormones. The hypothesis that cancer cells need excess cholesterol and intermediates of the cholesterol biosynthesis pathway to maintain a high level of proliferation is well accepted, however the mechanisms by which malignant cells and tissues reprogram cholesterol synthesis, uptake and efflux are yet to be fully elucidated as potential therapeutic targets. High and low density plasma lipoproteins are the likely major suppliers of cholesterol to cancer cells and tumors, potentially via receptor mediated mechanisms. This review is primarily focused on the role(s) of lipoproteins in carcinogenesis, and their future roles as drug delivery vehicles for targeted cancer chemotherapy.

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          Most cited references 64

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          On the origin of cancer cells.

           O WARBURG (1956)
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            A receptor-mediated pathway for cholesterol homeostasis.

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              How cells handle cholesterol.

               Kai Simons,  E. Ikonen (2000)
              Cholesterol plays an indispensable role in regulating the properties of cell membranes in mammalian cells. Recent advances suggest that cholesterol exerts many of its actions mainly by maintaining sphingolipid rafts in a functional state. How rafts contribute to cholesterol metabolism and transport in the cell is still an open issue. It has long been known that cellular cholesterol levels are precisely controlled by biosynthesis, efflux from cells, and influx of lipoprotein cholesterol into cells. The regulation of cholesterol homeostasis is now receiving a new focus, and this changed perspective may throw light on diseases caused by cholesterol excess, the prime example being atherosclerosis.
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                Author and article information

                Journal
                Front Pharmacol
                Front Pharmacol
                Front. Pharmacol.
                Frontiers in Pharmacology
                Frontiers Media S.A.
                1663-9812
                25 September 2013
                2013
                : 4
                Affiliations
                1Department of Molecular Biology and Immunology, University of North Texas Health Science Center Fort Worth, TX, USA
                2Department of Nutrition and Food Sciences, Texas Woman’s University Denton, TX, USA
                3LipoMedics Ltd. Co Fort Worth, TX, USA
                Author notes

                Edited by: Chao Lin, Tongji University, China

                Reviewed by: Marc Poirot, Institut National de la Santé et de la Recherche Médicale, France; Amit K. Tiwari, Tuskegee University, USA

                *Correspondence: Andras G. Lacko, Department of Molecular Biology and Immunology, University of North Texas Health Science Center, 3500 Camp Bowie Boulevard, Fort Worth, 76107 TX, USA e-mail: andras.lacko@ 123456unthsc.edu

                This article was submitted to Pharmacology of Anti-Cancer Drugs, a section of the journal Frontiers in Pharmacology.

                Article
                10.3389/fphar.2013.00119
                3782849
                24093019
                Copyright © Cruz, Mo, McConathy, Sabnis and Lacko.

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                Page count
                Figures: 0, Tables: 0, Equations: 0, References: 84, Pages: 7, Words: 0
                Categories
                Pharmacology
                Review Article

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