title: Antiproliferative effects of N-heterocyclic indolyl glyoxylamide derivatives on human lung cancer cells.
abstract: BACKGROUND
  N-Heterocyclic indolyl glyoxylamide compounds are derived from the antimicrotubule agent D-24851, which exhibits anticancer activity after oral administration. The actions of these compounds on lung cancer cells are still unknown. Here, we investigated the effects of two N-heterocyclic indolyl glyoxylamides, BPR0C259 and BPR0C123, on non-small human lung cancer cells.
  
  
  METHODS
  3-[4,5-dimethylthiazol-2-yl]2,5-diphenyltetrazolium bromide (MTT) assay was used to determine the half maximal inhibitory concentration (IC(50)), cell viability and radiation response of A549 cells and H1299 cells. Apoptosis was determined by sub-G(1) ratio, colony formation assay and caspase-3 activation. Cell cycle distribution was detected using flow cytometry.
  
  
  RESULTS
  Both compounds were able to inhibit the viability of human lung cancer cells, although the IC(50) of BPR0C123 was lower than that of BPR0C259. Both compounds induced significant sub-G1 and caspase-3 activation as low as 0.1 μM in both cell lines. These effects were independent of p53 activation because the level of serine-15 phosphorylated p53 was not affected after drug treatment. Furthermore, both compounds induced similar levels of G(2)/M phase arrest and radiosensitivity in these lung cancer cells.
  
  
  CONCLUSIONS
  Current data suggest that N-heterocyclic indolyl glyoxylamides can suppress the proliferation of and potentially increase radiosensitivity of human lung cancer cells.
authors.affiliation: Department of Biomedical Imaging and Radiological Sciences, National Yang-Ming University, No. 155, Linong St. Sec. 2, Beitou District, 112 Taipei, Taiwan, R.O.C.
authors.forename: Tien-Heng
authors.initials: TH
authors.lastname: Huang
authors.forename: Shu-Jun
authors.initials: SJ
authors.lastname: Chiu
authors.forename: Pei-Hsiuang
authors.initials: PH
authors.lastname: Chiang
authors.forename: Shih-Hwa
authors.initials: SH
authors.lastname: Chiou
authors.forename: Wen-Tai
authors.initials: WT
authors.lastname: Li
authors.forename: Chiung-Tong
authors.initials: CT
authors.lastname: Chen
authors.forename: C Allen
authors.initials: CA
authors.lastname: Chang
authors.forename: Jyh-Cheng
authors.initials: JC
authors.lastname: Chen
authors.forename: Yi-Jang
authors.initials: YJ
authors.lastname: Lee
mesh_terms: D017209:Apoptosis / Q000187:drug effects / Q000528:radiation effects; D002289:Carcinoma, Non-Small-Cell Lung / Q000473:pathology; D002455:Cell Division / Q000187:drug effects / Q000528:radiation effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects / Q000528:radiation effects; D002470:Cell Survival / Q000187:drug effects / Q000528:radiation effects; D004354:Drug Screening Assays, Antitumor; D016195:G2 Phase / Q000187:drug effects / Q000528:radiation effects; D006801:Humans; D007211:Indoles / Q000737:chemistry / Q000494:pharmacology*; D020128:Inhibitory Concentration 50; D008175:Lung Neoplasms / Q000473:pathology*; D011839:Radiation, Ionizing; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism
chemical_list: D007211:Indoles; D016159:Tumor Suppressor Protein p53