6533b852fe1ef96bd12aa405
RESEARCH PRODUCT
Cytotoxicity of sesquiterpene alkaloids from Nuphar plants toward sensitive and drug-resistant cell lines.
Noriko HayashiMasayuki YoshikawaSouichi NakashimaYoshikazu SugimotoMasashi FukayaMasashi FukayaHisashi MatsudaSeikou NakamuraMohamed-elamir F. HegazyThomas A. Efferthsubject
0301 basic medicineATP Binding Cassette Transporter Subfamily BTumor suppressor geneCell SurvivalATP-binding cassette transporterNuphar03 medical and health sciences0302 clinical medicineAlkaloidsCell Line TumorNeoplasmsATP Binding Cassette Transporter Subfamily G Member 2HumansATP Binding Cassette Transporter Subfamily B Member 1Binding siteCytotoxicityGeneOncogeneChemistryPlant ExtractsABCB5General MedicineMolecular biologyAntineoplastic Agents PhytogenicNeoplasm ProteinsGene Expression Regulation NeoplasticMolecular Docking Simulation030104 developmental biologyCell cultureDrug Resistance Neoplasm030220 oncology & carcinogenesisSesquiterpenesFood Sciencedescription
Multi-drug resistance (MDR) is a critical problem in cancer chemotherapy. MDR causes the overexpression of ATP-binding cassette (ABC) transporters and mutations in tumor suppressor genes and oncogenes. To tackle this issue, in this study, we focused on Nuphar plants, which have been traditionally used as food. Sesquiterpene alkaloids (1–3) were isolated from N. japonicum and dimeric sesquiterpene thioalkaloids (4–10) were isolated from N. pumilum. P-glycoprotein-overexpressing CEM/ADR5000 cells were cross-resistant to 6,6′-dihydroxythiobinupharidine (10). Using in silico molecular docking, we calculated the binding energies and simulated the interactions of these compounds with the corresponding amino acid residues at the binding site of P-gp. In addition, we investigated the cytotoxicity of these compounds towards cell lines overexpressing other ABC transporters (BCRP, ABCB5), cell lines with a knocked out tumor suppressor gene TP53 or cell lines overexpressing a deletion-activated EGFR oncogene. These cell lines were sensitive or only minimally cross-resistant to these compounds compared with their corresponding wild-type cell lines.
| year | journal | country | edition | language |
|---|---|---|---|---|
| 2018-11-09 | Foodfunction |