title: Evodiamine inhibits the proliferation of leukemia cell line K562 by regulating peroxisome proliferators-activated receptor gamma (PPARγ) pathway.
abstract: Evodiamine, a quinolone alkaloid, is one of the major bioactive compounds of Evodia rutaecarpa Bentham (Rutaceae). It exhibits excellent biological activities, especially the anticancer activity. This study aims to investigate the effect of evodiamine on the proliferation of leukemia cell line K562 and to explore the underlying mechanism. The effect of evodiamine on K562 cells proliferation was analyzed by trypan blue dye exclusion assay and MTT assay. The expression levels of peroxisome proliferators-activated receptor gamma (PPARγ), cyclin D1, and p21 were detected by western blot assay. The results demonstrated that evodiamine inhibited the proliferation and decreased the viability of K562 cells in a dose- and time-dependent manner. 2-Chloro-5-nitro-N-phenylbenzamide (GW9662) and/or PPARγ-siRNA pretreatment alleviated the cell growth suppression triggered by evodiamine. Meanwhile, evodiamine intervention elevated the expression of PPARγ in K562 cells, while pretreatment with GW9662 attenuated the enhanced upregulation of PPARγ expression induced by evodiamine. In addition, GW9662 and PPARγ-siRNA pretreatment also significantly attenuated the downregulation of the cell cycle control protein cyclin D1 and the upregulation of cyclin-dependent kinase inhibitor p21 induced by evodiamine. In conclusion, PPARγ signaling pathway may involve in the proliferation inhibition of evodiamine on K562 cells via inhibiting cylcin D1 and stimulating of p21.
authors.affiliation: a Department of Laboratory , Yantai Yuhuangding Hospital, Medical College, Qingdao University , Yantai , China and.
authors.forename: Chengming
authors.initials: C
authors.lastname: Sun
authors.affiliation: a Department of Laboratory , Yantai Yuhuangding Hospital, Medical College, Qingdao University , Yantai , China and.
authors.forename: Guili
authors.initials: G
authors.lastname: Zhang
authors.affiliation: b Department of Cardiology , Rongcheng Shidao People's Hospital , Rongcheng , China.
authors.forename: Shuping
authors.initials: S
authors.lastname: Luan
authors.affiliation: a Department of Laboratory , Yantai Yuhuangding Hospital, Medical College, Qingdao University , Yantai , China and.
authors.forename: Caifu
authors.initials: C
authors.lastname: Luan
authors.affiliation: a Department of Laboratory , Yantai Yuhuangding Hospital, Medical College, Qingdao University , Yantai , China and.
authors.forename: Huiyuan
authors.initials: H
authors.lastname: Shao
authors.affiliation: a Department of Laboratory , Yantai Yuhuangding Hospital, Medical College, Qingdao University , Yantai , China and.
authors.forename: Fei
authors.initials: F
authors.lastname: Dong
authors.affiliation: a Department of Laboratory , Yantai Yuhuangding Hospital, Medical College, Qingdao University , Yantai , China and.
authors.forename: Xuena
authors.initials: X
authors.lastname: Liu
mesh_terms: D000813:Anilides / Q000008:administration & dosage; D017209:Apoptosis / Q000187:drug effects; D002453:Cell Cycle / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D019938:Cyclin D1 / Q000096:biosynthesis* / Q000235:genetics; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000096:biosynthesis* / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D020014:K562 Cells; D007938:Leukemia / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D047495:PPAR gamma / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000235:genetics*; D011799:Quinazolines / Q000008:administration & dosage*
chemical_list: C457499:2-chloro-5-nitrobenzanilide; D000813:Anilides; C530104:CCND1 protein, human; D050759:Cyclin-Dependent Kinase Inhibitor p21; D047495:PPAR gamma; D011799:Quinazolines; D019938:Cyclin D1; C049639:evodiamine
keywords: Cyclin D1; K562 cells; PPARγ; evodiamine; p21