title: Atiprimod is an inhibitor of cancer cell proliferation and angiogenesis.
abstract: Atiprimod, a novel compound belonging to the azaspirane class of cationic amphiphilic drugs, exhibits both anti-proliferative and anti-angiogenic activities. Atiprimod inhibited proliferation of all human cancer cell lines included in the National Cancer Institute panel with IC50 values in the low micromolar range. Notably, metastatic cell lines were more sensitive to the compound compared to the non-metastatic cell lines derived from the same tumor tissue types. Atiprimod also induced apoptosis and activated both caspase-9 and caspase-3 in T84 colon carcinoma cells. Hence, the anti-proliferative activity could partly be due to its pro-apoptotic activity. Regarding angiogenesis in vitro, atiprimod inhibited both bFGF and VEGF induced proliferation and migration of human umbilical vein endothelial cells (HUVECs), resulting in disruption of cord formation. In addition, atiprimod also suppressed formation of new blood vessels in a chorioallantoic membrane assay. Previous studies have also shown that atiprimod treatment reduced production of IL-6, VEGF and inhibited activation of Stat3, a constitutively activated protein in majority of human cancers. Together these findings suggest that atiprimod acts on several molecules that are essential for tumor growth, invasion and metastasis.
authors.affiliation: Callisto Pharmaceuticals, Inc, 420 Lexington Avenue, Suite 1609, New York, NY 10170, USA. shailu@callistopharma.com
authors.forename: Kunwar
authors.initials: K
authors.lastname: Shailubhai
authors.forename: Surendra
authors.initials: S
authors.lastname: Dheer
authors.forename: Donald
authors.initials: D
authors.lastname: Picker
authors.forename: Gurmeet
authors.initials: G
authors.lastname: Kaur
authors.forename: Edward A
authors.initials: EA
authors.lastname: Sausville
authors.forename: Gary S
authors.initials: GS
authors.lastname: Jacob
mesh_terms: D020533:Angiogenesis Inhibitors / Q000494:pharmacology*; D017209:Apoptosis; D053148:Caspase 3; D053453:Caspase 9; D020169:Caspases / Q000378:metabolism; D002412:Cations; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D003094:Collagen / Q000494:pharmacology; D016207:Cytokines / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation; D004338:Drug Combinations; D004730:Endothelium, Vascular / Q000166:cytology; D004789:Enzyme Activation; D016222:Fibroblast Growth Factor 2 / Q000378:metabolism; D006801:Humans; D020128:Inhibitory Concentration 50; D007797:Laminin / Q000494:pharmacology; D008956:Models, Chemical; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D009369:Neoplasms / Q000188:drug therapy*; D009389:Neovascularization, Pathologic; D011509:Proteoglycans / Q000494:pharmacology; D050796:STAT3 Transcription Factor; D013141:Spiro Compounds / Q000494:pharmacology*; D015534:Trans-Activators / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
chemical_list: D020533:Angiogenesis Inhibitors; D002412:Cations; D016207:Cytokines; D004268:DNA-Binding Proteins; D004338:Drug Combinations; D007797:Laminin; D011509:Proteoglycans; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; D013141:Spiro Compounds; D015534:Trans-Activators; D042461:Vascular Endothelial Growth Factor A; D016222:Fibroblast Growth Factor 2; C059485:matrigel; C099015:azaspirane; D003094:Collagen; C505407:CASP3 protein, human; C506433:CASP9 protein, human; D053148:Caspase 3; D053453:Caspase 9; D020169:Caspases