title: Novel taspine derivative 12k inhibits cell growth and induces apoptosis in lung cell carcinoma.
abstract: Taspine is an active compound in anticancer agent development. 12k was synthesized with taspine as lead compound bearing biphenyl scaffold and showed potent anticancer activity. Here, we investigated the effect of taspine derivative 12k on A549 lung cells. We showed that 12k not only decreased significantly A549 cell viability, A549 cell colony formation but also impaired A549 cell migration. Moreover, 12k treatment blocked cell cycle progression by increasing cell number in S phase to 42.80% for 6 μmol/L vs. 28.86% for control while decreasing cell number in G1 phase. Accordingly, this was associated with an increase protein expression of cyclin E and a decrease protein expression of cyclin D1, cyclin B1 and its associated CDK1 (cdc2). Meanwhile, we found that 12k induced A549 cell apoptosis, which was closely associated with the effect of the Bcl-2 family. Increase of Bad, Bak and Bax expression levels, decrease of Bcl-2 and Mcl-1 expression levels were observed. SiRNA knockdown of c-myc in A549 cells significantly attenuated tumor inhibition effects of 12k. In conclusion, our results demonstrate that 12k has an inhibitory effect on growth of A549 cell by inducing cell cycle arrest and apoptosis.
authors.affiliation: School of Pharmacy, Health Science Center, Xi'an Jiaotong University, Xi'an 710061, PR China.
authors.forename: Bingling
authors.initials: B
authors.lastname: Dai
authors.affiliation: School of Pharmacy, Health Science Center, Xi'an Jiaotong University, Xi'an 710061, PR China.
authors.forename: Wenjie
authors.initials: W
authors.lastname: Wang
authors.affiliation: School of Pharmacy, Health Science Center, Xi'an Jiaotong University, Xi'an 710061, PR China.
authors.forename: Rui
authors.initials: R
authors.lastname: Liu
authors.affiliation: School of Pharmacy, Health Science Center, Xi'an Jiaotong University, Xi'an 710061, PR China.
authors.forename: Hongying
authors.initials: H
authors.lastname: Wang
authors.affiliation: School of Pharmacy, Health Science Center, Xi'an Jiaotong University, Xi'an 710061, PR China. Electronic address: zhang2008@mail.xjtu.edu.cn.
authors.forename: Yanmin
authors.initials: Y
authors.lastname: Zhang
mesh_terms: D000470:Alkaloids / Q000737:chemistry* / Q000494:pharmacology / Q000627:therapeutic use*; D017209:Apoptosis / Q000187:drug effects* / Q000502:physiology; D002453:Cell Cycle / Q000187:drug effects / Q000502:physiology; D045744:Cell Line, Tumor; D004305:Dose-Response Relationship, Drug; D006131:Growth Inhibitors / Q000737:chemistry* / Q000494:pharmacology / Q000627:therapeutic use*; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000473:pathology
chemical_list: D000470:Alkaloids; D006131:Growth Inhibitors; C018394:taspine
keywords: 12k; A549 cells; Apoptosis; Cell cycle