title: A receptor tyrosine kinase inhibitor, Tyrphostin A9 induces cancer cell death through Drp1 dependent mitochondria fragmentation.
abstract: Mitochondria dynamics controls not only their morphology but also functions of mitochondria. Therefore, an imbalance of the dynamics eventually leads to mitochondria disruption and cell death. To identify specific regulators of mitochondria dynamics, we screened a bioactive chemical compound library and selected Tyrphostin A9, a tyrosine kinase inhibitor, as a potent inducer of mitochondrial fission. Tyrphostin A9 treatment resulted in the formation of fragmented mitochondria filament. In addition, cellular ATP level was decreased and the mitochondrial membrane potential was collapsed in Tyr A9-treated cells. Suppression of Drp1 activity by siRNA or over-expression of a dominant negative mutant of Drp1 inhibited both mitochondrial fragmentation and cell death induced by Tyrpohotin A9. Moreover, treatment of Tyrphostin A9 also evoked mitochondrial fragmentation in other cells including the neuroblastomas. Taken together, these results suggest that Tyrphostin A9 induces Drp1-mediated mitochondrial fission and apoptotic cell death.
authors.affiliation: Graduate School of East-West Medical Science, Kyung Hee University, Gyeoggi-Do 446-701, Republic of Korea.
authors.forename: So Jung
authors.initials: SJ
authors.lastname: Park
authors.forename: Young Jun
authors.initials: YJ
authors.lastname: Park
authors.forename: Ji Hyun
authors.initials: JH
authors.lastname: Shin
authors.forename: Eun Sung
authors.initials: ES
authors.lastname: Kim
authors.forename: Jung Jin
authors.initials: JJ
authors.lastname: Hwang
authors.forename: Dong-Hoon
authors.initials: DH
authors.lastname: Jin
authors.forename: Jin Cheon
authors.initials: JC
authors.lastname: Kim
authors.forename: Dong-Hyung
authors.initials: DH
authors.lastname: Cho
mesh_terms: D017209:Apoptosis; D034281:Dynamins; D020558:GTP Phosphohydrolases / Q000235:genetics / Q000378:metabolism*; D006367:HeLa Cells; D006801:Humans; D008869:Microtubule-Associated Proteins / Q000235:genetics / Q000378:metabolism*; D008928:Mitochondria / Q000187:drug effects*; D024101:Mitochondrial Proteins / Q000235:genetics / Q000378:metabolism*; D009369:Neoplasms / Q000201:enzymology*; D047428:Protein Kinase Inhibitors / Q000494:pharmacology*; D020794:Receptor Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors*; D020032:Tyrphostins / Q000494:pharmacology*
chemical_list: D008869:Microtubule-Associated Proteins; D024101:Mitochondrial Proteins; D047428:Protein Kinase Inhibitors; D020032:Tyrphostins; C406122:tyrphostin A9; D020794:Receptor Protein-Tyrosine Kinases; D020558:GTP Phosphohydrolases; C110768:DNM1L protein, human; D034281:Dynamins