RRC ID 39145
著者 Mapoung S, Pitchakarn P, Yodkeeree S, Ovatlarnporn C, Sakorn N, Limtrakul P.
タイトル Chemosensitizing effects of synthetic curcumin analogs on human multi-drug resistance leukemic cells.
ジャーナル Chem Biol Interact
Abstract Curcumin analogs were synthesized and their multi-drug resistance (MDR) reversing properties were determined in human MDR leukemic (K562/Adr) cells. Four analogs, 1,7-bis-(3,4-dimethoxy-phenyl)-hepta-1,6-diene-3,5-dione (1J), 2,6-bis-(4-hydroxy-3-methoxy-benzylidene)-cyclohexanone (2A), 2,6-bis-(3,4-dihydroxy-benzylidene)-cyclohexanone (2F) and 2,6-bis-(3,4-dimethoxy-benzylidene)-cyclohexanone (2J) markedly increased the sensitivity of K562/Adr cells to paclitaxel (PTX) for 8-, 2-, 8- and 16- folds, respectively and vinblastine (Vin) for 5-, 3-, 12- and 30- folds, respectively. The accumulation of P-gp substrates, Calcein-AM, Rhodamine 123 and Doxorubicin, was significantly increased by 1J (up to 6-, 11- and 22- folds, respectively) and 2J (up to 7-, 12- and 17- folds, respectively). Besides 2A, 2F and 2J dramatically decreased P-gp expression in K562/Adr cells. These results could be summarized in the following way. Analog 1J inhibited only P-gp function, while 2A and 2F inhibited only P-gp expression. Interestingly, 2J exerts inhibition of both P-gp function and expression. The combination index (CI) of combination between 2J and PTX (0.09) or Vin (0.06) in K562/Adr cells indicated strong synergistic effects, which likely due to its MDR reversing activity. Moreover, these analogs showed less cytotoxicity to peripheral mononuclear cells (human) and red blood cells (human and rat) suggesting the safety of analogs for further animal and clinical studies.
巻・号 244
ページ 140-8
公開日 2016-1-25
DOI 10.1016/j.cbi.2015.12.001
PII S0009-2797(15)30136-8
PMID 26689174
MeSH ATP Binding Cassette Transporter, Subfamily B, Member 1 / antagonists & inhibitors ATP Binding Cassette Transporter, Subfamily B, Member 1 / biosynthesis ATP Binding Cassette Transporter, Subfamily B, Member 1 / metabolism Animals Antineoplastic Agents / chemical synthesis Antineoplastic Agents / chemistry Antineoplastic Agents / pharmacology* Cell Survival / drug effects Curcumin / analogs & derivatives* Curcumin / chemical synthesis Curcumin / chemistry Curcumin / pharmacology* Dose-Response Relationship, Drug Drug Resistance, Multiple / drug effects* Drug Resistance, Neoplasm / drug effects* Erythrocytes / drug effects Humans K562 Cells Leukemia / drug therapy* Leukemia / pathology* Leukocytes, Mononuclear / drug effects Molecular Structure Rats Solubility Structure-Activity Relationship Tumor Cells, Cultured
IF 3.723
引用数 23
WOS 分野 PHARMACOLOGY & PHARMACY TOXICOLOGY BIOCHEMISTRY & MOLECULAR BIOLOGY
リソース情報
ヒト・動物細胞 K562/Adr(RCB1898)