Painting with a molecular brush: genomic/proteomic interfacing to define the drug action profile of novel solid-tumor selective anticancer agents.
XK469 is an investigational anticancer agent that exhibits antiproliferative activity in tumor-bearing animal models. We examined the drug-action profile of this agent at the molecular level regarding alterations induced in gene expression and proteins in HCT-116 human colon adenocarcinoma cells. We used a unique cDNA microarray (GeneMap(TM) Cancerarray) comprising 1152 human tumor-related genes and 2-D gel electrophoresis, respectively, following a 24-hour exposure to a drug concentration that killed a two-log fraction of HCT-116 clonogenic cells. Functional gene cluster profile (FGCP) analysis of the 71 out of 1152 genes that displayed a >2-fold increase or decrease in expression (over untreated control) identified a drug-specific involvement of the MAPK signal transduction pathway. MAPK signaling together with the involvement of ubiquitin proteins from 2-D gel electrophoresis suggest a novel drug-action profile at the molecular level for the in vitro antiproliferative activity of XK469.
Nakeff
Alexander
A
Drug Discovery and Development Program, Josephine Ford Cancer Center, Henry Ford Health System, Detroit, Michigan 48202, USA.
Sahay
Nisha
N
Pisano
Mike
M
Subramanian
Balanehru
B
D000230:Adenocarcinoma / Q000235:genetics*; D000970:Antineoplastic Agents / Q000494:pharmacology*; D003110:Colonic Neoplasms / Q000235:genetics*; D020869:Gene Expression Profiling; D006801:Humans; D020935:MAP Kinase Signaling System / Q000235:genetics; D005810:Multigene Family; D009363:Neoplasm Proteins / Q000032:analysis; D020543:Proteome / Q000235:genetics*; D011810:Quinoxalines / Q000494:pharmacology*
D000970:Antineoplastic Agents; D009363:Neoplasm Proteins; D020543:Proteome; D011810:Quinoxalines; C118180:XK 469