title: P-glycoprotein and its inhibition in tumors by phytochemicals derived from Chinese herbs.
abstract: P-glycoprotein belongs to the family of ATP-binding cassette (ABC) transporters. It functions in cellular detoxification, pumping a wide range of xenobiotic compounds, including anticancer drugs out of the cell. In cancerous cells, P-glycoprotein confers resistance to a broad spectrum of anticancer agents, a phenomenon termed multidrug resistance. An attractive strategy for overcoming multidrug resistance is to block the transport function of P-glycoprotein and thus increase intracellular concentrations of anticancer drugs to lethal levels. Efforts to identify P-glycoprotein inhibitors have led to numerous candidates, none of which have passed clinical trials with cancer patients due to their high toxicity. The search for naturally inhibitory products from traditional Chinese medicine may be more promising because natural products are frequently less toxic than chemically synthesized substances. In this review, we give an overview of molecular and clinical aspects of P-glycoprotein and multidrug resistance in the context of cancer as well as Chinese herbs and phytochemicals showing inhibitory activity towards P-glycoprotein.
authors.affiliation: Department of Pharmaceutical Biology, Institute of Pharmacy and Biochemistry, Johannes Gutenberg University, Mainz, Germany.
authors.forename: Tolga
authors.initials: T
authors.lastname: Eichhorn
authors.forename: Thomas
authors.initials: T
authors.lastname: Efferth
mesh_terms: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000037:antagonists & inhibitors* / Q000378:metabolism; D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000009:adverse effects / Q000627:therapeutic use*; D019008:Drug Resistance, Neoplasm; D004365:Drugs, Chinese Herbal / Q000009:adverse effects / Q000627:therapeutic use*; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D010946:Plants, Medicinal
chemical_list: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000972:Antineoplastic Agents, Phytogenic; D004365:Drugs, Chinese Herbal