A receptor tyrosine kinase inhibitor, Tyrphostin A9 induces cancer cell death through Drp1 dependent mitochondria fragmentation

作者：Park So Jung; Park Young Jun; Shin Ji Hyun; Kim Eun Sung; Hwang Jung Jin; Jin Dong Hoon; Kim Jin Cheon; Cho Dong Hyung^*

来源：Biochemical and Biophysical Research Communications, 2011, 408(3): 465-470.

DOI：10.1016/j.bbrc.2011.04.053

• Mitochondria dynamics
• Fission
• Tyrphositn A9
• Apoptosis

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.

• 出版日期2011-5-13