Expression systems of cytochrome P450 proteins in studies of drug metabolism in vitro
Journal Title: Advances in Hygiene and Experimental Medicine - Year 2011, Vol 65, Issue 0
Abstract
Cytochrome P450 proteins are the most important enzymes involved in metabolic activation or detoxification of various drugs used in clinical practice. However, some drug metabolism pathways may be responsible for their increased toxicity. New expression systems of cytochrome P450 proteins in mammalian cells, including human, are designed to explore the influence of metabolism on the cellular and molecular mechanisms of action of potential drugs and those used therapeutically. They can also be used to study the effect of tested compounds on activity and expression of metabolizing enzymes. Human tumor cell lines with overexpression of cytochrome P450 isoenzymes are of particular importance, especially in studies of potential chemotherapeutics. The HepG2 cell line, derived from human liver cancer, is the most commonly used in studies on drug metabolism and toxicity. However, due to the low level of metabolizing enzymes in these cells, the Hep3A4 cell line with overexpression of CYP3A4 isoenzyme was developed. The stable overexpression of cytochrome P450 isoenzymes was also obtained in other human cancer cell lines, including hepatoma HepaRG cells, ovarian cancer IGROV-1 cells, colon cancer Caco-2, and LS180 cells. This review describes currently developed bacterial, yeast, insect and mammalian (including human) cytochrome P450 protein expression systems, in terms of their advantages and disadvantages in the context of their suitability for basic research and use on a commercial scale.
Authors and Affiliations
Monika Pawłowska, Ewa Augustin
Keywords
Related Articles
- EP ID EP66490
- DOI -
- Views 144
- Downloads 0
Nadzór nad grypą
Nadzór nad grypą został zainicjowany w 1947 r., od tego czasu Światowa Organizacja Zdrowia (WHO - World Health Organization) koordynuje współpracę międzynarodową, mając na celu monitorowanie aktywności wirusów grypy, sku...
Glycated albumin as a marker of glycemia in diabetes and its vascular complications
Effective glycemic control is very important to prevent the onset and the progression of chronic complications in diabetic patients. It is known that glycation of various proteins is increased in diabetic patients compar...
The role of metalloproteinases in modification of extracellular matrix in invasive tumor growth, metastasis and angiogenesis
Extracellular matrix metalloproteinases (MMPs) are a family of endopeptydases which recquire a zinc ion at their active site, for proteolityc activity. There are six members of the MMP family: matrilysins, collagenases,...
Okołodobowe stężenia wolnego testosteronu, wybranych markerów metabolizmu kostnego, osteoprotegeryny i jej ligandu sRANKL u otyłych kobiet po menopauzie
Wstęp: Istnieją sugestie, że zwiększone wytwarzanie testosteronu u otyłych kobiet po menopauzie może wpływać ochronnie na tkankę kostną, a istotną rolę w mechanizmie tych zależności pełni najprawdopodobniej system RANKL/...
Irisin – a new mediator of energy homeostasis
Skeletal muscles as an active hormonal compartment in the response of physical activity secrete substances named myokines capable of modulating metabolic processes. Myokines take part in communication between muscles and...