title: BME, a novel compound of anthraquinone, down regulated P-glycoprotein expression in doxorubicin-resistant human myelogenous leukemia (K562/DOX) cells via generation of reactive oxygen species.
abstract: P-glycoprotein (P-gp)-mediated multidrug resistance (MDR) in tumor cells is still a main obstacle for the chemotherapeutic treatment of cancers. Thus, development of effective MDR reversing agents is an important approach in the clinic. The present study revealed that BME, a novel compound of anthraquinone, elevated intracellular accumulation of the P-gp substrates and reduced concentration resulting in 50% inhibition of cell growth (IC50) values for doxorubicin (DOX) in doxorubicin-resistant human myelogenous leukemia (K562/DOX) cells. Further more, BME was also reported to down regulated P-gp expression accompanying with generation of nontoxic low level of intracellular reactive oxygen species (iROS) and activation of extracellular signal-regulated kinase (ERK)1/2 as well as c-JUN N-terminal kinase (JNK). However, treatment with N-acetyl-cysteine (NAC), U0216 and SP600125 almost abolished actions of the BME mentioned above. These results indicated that the effect of the BME on the P-gp may be involved in generation of nontoxic low level of iROS and activation of ERK1/2 or JNK, which suggested valuable clues to screen and develop P-gp reversing agents.
authors.affiliation: Key Laboratory of Natural Medicine and Immune Engineering, Henan University, Kaifeng 475001, China.
authors.forename: Jianhong
authors.initials: J
authors.lastname: Wang
authors.affiliation: Key Laboratory of Natural Medicine and Immune Engineering, Henan University, Kaifeng 475001, China.
authors.forename: Lu
authors.initials: L
authors.lastname: Liu
authors.affiliation: Key Laboratory of Natural Medicine and Immune Engineering, Henan University, Kaifeng 475001, China.
authors.forename: Juan
authors.initials: J
authors.lastname: Cen
authors.affiliation: Key Laboratory of Natural Medicine and Immune Engineering, Henan University, Kaifeng 475001, China. Electronic address: jibiansheng2005@126.com.
authors.forename: Biansheng
authors.initials: B
authors.lastname: Ji
mesh_terms: D018435:ATP Binding Cassette Transporter, Subfamily B / Q000378:metabolism*; D000880:Anthraquinones / Q000737:chemistry* / Q000494:pharmacology*; D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology*; D002453:Cell Cycle / Q000187:drug effects; D015536:Down-Regulation / Q000187:drug effects; D004317:Doxorubicin / Q000493:pharmacokinetics / Q000494:pharmacology*; D019008:Drug Resistance, Neoplasm / Q000187:drug effects*; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D006801:Humans; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism; D020014:K562 Cells / Q000187:drug effects / Q000378:metabolism; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism*; D020112:Rhodamine 123 / Q000378:metabolism
chemical_list: D018435:ATP Binding Cassette Transporter, Subfamily B; D000880:Anthraquinones; D000970:Antineoplastic Agents; D017382:Reactive Oxygen Species; D020112:Rhodamine 123; D004317:Doxorubicin; D048049:Extracellular Signal-Regulated MAP Kinases; D048031:JNK Mitogen-Activated Protein Kinases; C535150:MAPK1 protein, human; D019950:Mitogen-Activated Protein Kinase 1
keywords: BME; P-glycoprotein; Reactive oxygen species