Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P33527 (ABCC1)
 1,164 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Here we showed that bivalency approach is effective in modulating multidrug resistance protein 1 (MRP1/ABCC1)-mediated doxorubicin (DOX) and etoposide (VP16) resistance in human 2008/MRP1 ovarian carcinoma cells. Flavonoid dimers bearing five or six ethylene glycol (EG) units with 6-methyl (4e, 4f) or 7-methyl (5e, 5f) substitution on the ring A of flavonoid dimers have the highest modulating activity for DOX against MRP1 with an EC(50) ranging from 73 to 133 nM. At 0.5 microM, the flavonoid dimer 4e was sufficient to restore DOX accumulation in 2008/MRP1 to parental 2008/P level. Lineweaver-Burk and Dixon plot suggested that it is likely a competitive inhibitor of DOX transport with a K(i) = 0.2 microM. Our data suggest that flavonoid dimers have a high affinity toward binding to DOX recognition site of MRP1. This results in inhibiting DOX transport, increasing intracellular DOX retention, and finally resensitizing 2008/MRP1 to DOX. The present study demonstrates that flavonoid dimers can be employed as an effective modulator of MRP1-mediated drug resistance in cancer cells.
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PMID:Modulation of multidrug resistance protein 1 (MRP1/ABCC1)-mediated multidrug resistance by bivalent apigenin homodimers and their derivatives. 1972 78

The unique aroma and flavor of oolong tea develop during the withering stage of postharvest processing. We explored the roles of miRNA-related regulatory networks during tea withering and their effects on oolong tea quality. We conducted transcriptome and miRNA analyses to identify differentially expressed (DE) miRNAs and target genes among fresh leaves, indoor-withered leaves, and solar-withered leaves. We identified 32 DE-miRNAs and 41 target genes involved in phytohormone signal transduction and ABC transporters. Further analyses indicated that these two pathways regulated the accumulation of flavor-related metabolites during tea withering. Flavonoid accumulation was correlated with the miR167d_1-ARF-GH3, miR845-ABCC1-3/ABCC2, miR166d-5p_1-ABCC1-2, and miR319c_3-PIF-ARF modules. Terpenoid content was correlated with the miR171b-3p_2-DELLA-MYC2 and miR166d-5p_1-ABCG2-MYC2 modules. These modules inhibited flavonoid biosynthesis and enhanced terpenoid biosynthesis in solar-withered leaves. Low auxin and gibberellic acid contents and circRNA-related regulatory networks also regulated the accumulation of flavor compounds in solar-withered leaves. Our analyses reveal how solar withering produces high-quality oolong tea.
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PMID:Integrated Transcriptome, microRNA, and Phytochemical Analyses Reveal Roles of Phytohormone Signal Transduction and ABC Transporters in Flavor Formation of Oolong Tea (Camellia sinensis) during Solar Withering. 3311 39