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The multidrug resistance (MDR) proteins that belong to the ATP-binding cassette superfamily such as P-glycoprotein (P-gp) and MRP1, are present in a majority of human tumors and constitute an important cause of therapeutic failure. Selective inhibitors of the MDR-efflux proteins may improve the effectiveness of cancer chemotherapy. Their mechanism of action was believed to be a competition between resistance modifiers and drugs for the same binding site of P-gp. In our previous work we studied modulation of MDR in cancer cells expressing P-gp or MRP1 by selected carotenoids, flavonoids and extracts from medically important Chinese plants. Capsanthin and capsorubin, carotenoids isolated from paprika, were identified as potent P-gp inhibitors, while lycopene, lutein, antheraxanthin and violaxanthin induced moderate effects. Among flavonoids, effective modulators were rotenone, chrysin, phloretin and sakuranetin. Some chloroform extracts of Chinese herbs were also found to inhibit MDR efflux pumps. The effects of the modulators on P-gp activity were studied by measuring rhodamine 123 uptake in several cancer cells such as the human MDR1 gene-transfected mouse lymphoma cells (L1210) and human breast cancer cells MDA-MB-231 expressing the MRP1 pump (HTB26). Additionally, the ability to alter biophysical properties of lipid bilayers by selected carotenoids was studied by differential scanning calorimetry. The antiproliferative effects as well as the MDR reversal activity of the studied compounds, applied in combination with anticancer drugs, were also discussed.
Institute of Medical Microbiology and Immunobiology, University of Szeged, H-6720 Szeged, Dóm tér 10. Hungary. firstname.lastname@example.org.
This article was published in the following journal.
Name: Current topics in medicinal chemistry
Natural substances, particularly medicinal plants and their extracts, are still today intended as source for new Active Pharmaceutical Ingredients (APIs). Alternatively they can be validly employed to...
Identification of Important Compounds Isolated from Natural Sources that Have Activity Against Multidrug-resistant Cancer Cell Lines: Effects on Proliferation, Apoptotic Mechanism and the Efflux Pump Responsible for Multi-resistance Phenotype.
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The science of drugs prepared from natural-sources including preparations from PLANTS, animals, and other organisms as well as MINERALS and other substances included in MATERIA MEDICA. The therapeutic usage of plants is PHYTOTHERAPY.
Procedures to reverse the effect of REPRODUCTIVE STERILIZATION and to regain fertility. Reversal procedures include those used to restore the flow in the FALLOPIAN TUBE or the VAS DEFERENS.
Toxic substances from microorganisms, plants or animals that interfere with the functions of the nervous system. Most venoms contain neurotoxic substances. Myotoxins are included in this concept.
Complete or partial change from one sex to another with regard to gonadal development. Gonadal sex reversal may occur naturally or be induced by factors such as steroids, temperature, and autosomal abnormalities during the critical period of gonadal differentiation (SEX DIFFERENTIATION) in some species.
Specific substances elaborated by plants, microorganisms or animals that cause damage to the skin; they may be proteins or other specific factors or substances; constituents of spider, jellyfish or other venoms cause dermonecrosis and certain bacteria synthesize dermolytic agents.
Cancer is not just one disease but many diseases. There are more than 100 different types of cancer. Most cancers are named for the organ or type of cell in which they start - for example, cancer that begins in the colon is called colon cancer; cancer th...
Bladder Cancer Brain Cancer Breast Cancer Cancer Cervical Cancer Colorectal Head & Neck Cancers Hodgkin Lymphoma Leukemia Lung Cancer Melanoma Myeloma Ovarian Cancer Pancreatic Cancer ...
Head and neck cancers
Cancer can occur in any of the tissues or organs in the head and neck. There are over 30 different places that cancer can develop in the head and neck area. Mouth cancers (oral cancers) - Mouth cancer can develop on the lip, the tongue, the floor...