title: Reversal of human multi-drug resistance leukaemic cells by stemofoline derivatives via inhibition of P-glycoprotein function.
abstract: Our previous study reported multi-drug resistance (MDR) reversing properties of synthetic stemofoline derivatives (STFD), OH-A1, NH-B6 and NH-D6 on P-glycoprotein (P-gp) overexpressing leukaemic cells (K562/Adr); however, the mechanism was unclear. In this study, we further investigated whether the STFD reverse MDR through either the inhibition of P-gp function or expression in K562/Adr cells, or both. The P-gp functional studies showed that the STFD increased the accumulation of calcein-AM, rhodamine 123 and [(14) C]-doxorubicin in K562/Adr cells, while the effects have not been seen in their parental sensitive cancer cell line (K562). Further, the STFD did not alter the P-gp expression as determined by Western blotting. This study concludes that the STFD reverse MDR via the inhibition of P-gp function. The efficacy of the STFD to inhibit P-gp function followed the order: NH-B6 > OH-A1 > NH-D6. These compounds could be introduced as candidate molecules for treating cancers exhibiting P-gp-mediated MDR.
authors.affiliation: Department of Biochemistry, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand.
authors.forename: Sonthaya
authors.initials: S
authors.lastname: Umsumarng
authors.forename: Pornsiri
authors.initials: P
authors.lastname: Pitchakarn
authors.forename: Kwankamol
authors.initials: K
authors.lastname: Sastraruji
authors.forename: Supachai
authors.initials: S
authors.lastname: Yodkeeree
authors.forename: Alison T
authors.initials: AT
authors.lastname: Ung
authors.forename: Stephen G
authors.initials: SG
authors.lastname: Pyne
authors.forename: Pornngarm
authors.initials: P
authors.lastname: Limtrakul
mesh_terms: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D000970:Antineoplastic Agents / Q000494:pharmacology*; D059447:Cell Cycle Checkpoints / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D018432:Drug Resistance, Multiple / Q000187:drug effects*; D019008:Drug Resistance, Neoplasm / Q000187:drug effects*; D006576:Heterocyclic Compounds, 4 or More Rings / Q000494:pharmacology* / Q000633:toxicity; D006801:Humans; D020014:K562 Cells; D004915:Leukemia, Erythroblastic, Acute / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism / Q000473:pathology
chemical_list: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000970:Antineoplastic Agents; D006576:Heterocyclic Compounds, 4 or More Rings; C430220:stemofoline