Multidrug resistance (MDR) is a major challenge in cancer treatment, and the breast cancer resistance protein (BCRP) is an important target in the search for new MDR-reversing drugs. With the aim of discovering new potential BCRP inhibitors, the crude extract of leaves of Eremophila galeata, a plant endemic to Australia, was investigated for inhibitory activity of parental (HT29par) as well as BCRP-overexpressing HT29 colon cancer cells resistant to the chemotherapeutic SN-38 (i.e., HT29SN38 cells). This identified a fraction, eluted with 40% acetonitrile on a solid-phase extraction column, which showed weak growth-inhibitory activity on HT29SN38 cells when administered alone, but exhibited concentration-dependent growth inhibition when administered in combination with SN-38. The major constituent in this fraction was isolated and found to be 5,3′,5′-trihydroxy-3,6,7,4′-tetramethoxyflavone (2), which at a concentration of 25 μg/mL potentiated the growth-inhibitory activity of SN-38 to a degree comparable to that of the known BCRP inhibitor Ko143 at 1 μM. A dye accumulation experiment suggested that 2 inhibits BCRP, and docking studies showed that 2 binds to the same BCRP site as SN-38. These results indicate that 2 acts synergistically with SN-38, with 2 being a BCRP efflux pump inhibitor while SN-38 inhibits topoisomerase-1.
Multiple Sclerosis (MS) is a demyelinating disease affecting the central nervous system, with no curative medicine available. The use of herbal drugs and dietary supplements is increasing among people with MS (PwMS), raising a need for knowledge about potential interactions between conventional MS medicine and herbal drugs/ dietary supplements. This systematic review provides information about the safety of simultaneous use of conventional MS-drugs and herbal drugs frequently used by PwMS. The study included 14 selected disease-modifying treatments and drugs frequently used for symptom-alleviation. A total of 129 published papers found via PubMed and Web of Science were reviewed according to defined inclusion-and exclusion criteria. Findings suggested that daily recommended doses of Panax ginseng and Ginkgo biloba should not be exceeded, and herbal preparations differing from standardized products should be avoided, especially when combined with anticoagulants or substrates of certain cytochrome P450 isoforms. Further studies are required regarding ginseng's ability to increase aspirin bioavailability. Combinations between chronic cannabis use and selective serotonin reuptake inhibitors or non-steroidal antiinflammatory drugs should be carefully monitored, whereas no significant evidence for drug-interactions between conventional MS-drugs and ginger, cranberry, vitamin D, fatty acids, turmeric, probiotics or glucosamine was found.
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