title: 8-(Tosylamino)quinoline inhibits tumour progression through targeting phosphoinositide-3-kinase/Akt pathway.
abstract: We examined whether 8-(tosylamino)quinoline (8-TQ), a structural analogue of BAY 11-7082, is able to modulate various tumourigenic responses using various in vitro and in vivo experimental conditions. 8-TQ exhibited the strongest suppressive activity on the proliferation of C6, A431, HeLa and MDA-MB-231 cells with IC550 values ranging from 10 to 30 microM. According to the analysis of level of active caspase-3, and morphologies of C6, HeLa and MDA-MB-231 cells, it was revealed that 8-TQ is able to induce apoptosis. Furthermore, this compound strongly diminished the invasion of MDA-MB-231 cells, the migration of HeLa cells, and the new generation of blood vessels under non-toxic conditions. Reduction of the phospho-form levels of intracellular signalling enzymes by 8-TQ strongly indicated that molecular signalling machineries composed of phosphoinositide 3-kinase (PI3K)/phosphoinositide-dependent kinase-1 (PDK1)/Akt and extracellular-signal-regulated kinase (ERK) could be targeted by 8-TQ treatment. Indeed, the specific inhibitors (LY294002 and U0126) of PI3K/PDK1/Akt and ERK showed similar anti-cancer properties to 8-TQ. Finally, 8-TQ intraperitoneally injected suppressed the increase of tumour volume up to 40% compared to vehicle-treated control. Taken together, our results clearly suggest that 8-TQ might have applications as a novel anti-cancer drug or may be served as a lead compound to be further optimized.
authors.affiliation: Department of Genetic Engineering, Sungkyunkwan University, Suwon, Republic of Korea.
authors.forename: Yongwoo
authors.initials: Y
authors.lastname: Jung
authors.forename: Young-Su
authors.initials: YS
authors.lastname: Yi
authors.forename: Dae Sung
authors.initials: DS
authors.lastname: Yoo
authors.forename: Ji Hye
authors.initials: JH
authors.lastname: Kim
authors.forename: Woo Seok
authors.initials: WS
authors.lastname: Yang
authors.forename: Jongsung
authors.initials: J
authors.lastname: Lee
authors.forename: Kye Won
authors.initials: KW
authors.lastname: Park
authors.forename: Dae-Hyuk
authors.initials: DH
authors.lastname: Kweon
authors.forename: Sungyoul
authors.initials: S
authors.lastname: Hong
authors.forename: Jae Youl
authors.initials: JY
authors.lastname: Cho
mesh_terms: D020533:Angiogenesis Inhibitors / Q000627:therapeutic use; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D015153:Blotting, Western; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D049033:Chorioallantoic Membrane / Q000187:drug effects; D018450:Disease Progression; D006801:Humans; D047468:Immunoprecipitation; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018613:Microscopy, Confocal; D009361:Neoplasm Invasiveness; D009389:Neovascularization, Pathologic / Q000188:drug therapy; D051058:Oncogene Protein v-akt / Q000502:physiology*; D019869:Phosphatidylinositol 3-Kinases / Q000502:physiology*; D011804:Quinolines / Q000494:pharmacology*; D014105:Tosyl Compounds / Q000494:pharmacology*; D014945:Wound Healing / Q000187:drug effects
chemical_list: C579515:8-(tosylamino)quinoline; D020533:Angiogenesis Inhibitors; D000970:Antineoplastic Agents; D011804:Quinolines; D014105:Tosyl Compounds; D019869:Phosphatidylinositol 3-Kinases; D051058:Oncogene Protein v-akt; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9