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

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.

ATP‑binding cassette transporter A1: A promising therapy target for prostate cancer (Review)

“…Moreover, low serum cholesterol levels have been found in prostate cancer patients, suggesting that cholesterol may accumulate in tumor tissue. Compared with normal prostate cells, prostate tumor cells exhibit increased levels of intracellular cholesterol precursors, with loss of ABCA1-mediated cholesterol efflux (5).…”

Steroid-photosensitizer conjugates: Syntheses and applications

“…Bonar-Law and Sanders [64] prepared several porphyrin-based receptors which employ the 7,24-cyclo [2]cholate as a structural and recognition element. The synthesis of two types of semisynthetic receptors composed of porphyrins capped on one or both faces by a 7,24-cyclo [2]cholate (e.g. 74 and 75) are reported.…”

“…To this end they prepared complex 46 by coupling testosterone, modified with an arm bearing a cleavable disulfide bridge (45) and a,a-5,10-bis-[{o-(2-carboxyethyl)carboxamido}phenyl]-15,20-diphenylporphyrin (44), followed by metalation with Mn(OAc) 2 .…”

“…The most abundant steroid in humans is highly lipophilic cholesterol, which is conjugated to fatty acids and constitutes the main component of cell membranes in animals and microorganisms [2]. Cholesterol is the precursor of the bile acids in the liver and the starting material for the biosynthesis of steroid hormones.…”

“…The major classes of steroid hormones are: (a) progestogens, including (1) progesterone which regulates cyclical changes in the endometrium of the uterus and maintains pregnancy, and corticosteroids (corticoids), (2) aldosterone that helps regulate blood pressure and (3) cortisol, a glucocorticoid, the functions of which include immune suppression; (b) androgens including testosterone which contributes to the development and maintenance of male secondary sex characteristics; and (c) estrogens that contribute to the development and maintenance of female secondary sex characteristics. Human steroidogenesis occurs in a number of locations throughout the body.…”