Necrostatin-1 reverts shikonin-induced necroptosis to apoptosis.
Degterev et al. previously demonstrated that death receptor mediated apoptosis could be diverted to necroptosis when apoptosis signaling was blocked, suggesting that necroptosis may function as a backup mechanism to insure the elimination of damaged cells under certain conditions when apoptosis was inhibited. Here, we show that shikonin-induced necroptosis can be reverted to apoptosis in the presence of necrostatin-1 (Nec-1), a specific necroptosis inhibitor and that the death mode switch is at least partially due to the conversion from mitochondrial inner membrane permeability to mitochondrial outer membrane permeability, which is associated with Bax translocation. The data combined with the previous reports support a notion that apoptosis and necroptosis may function as reciprocal backup mechanisms of cellular demise. To the best of our knowledge, this is the first study to document a conversion from necroptosis to apoptosis.
Han
Weidong
W
Cancer Institute, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, 310009, China. hanweidong1979@gmail.com.
Xie
Jiansheng
J
Li
Ling
L
Liu
Zhen
Z
Hu
Xun
X
D017209:Apoptosis / Q000187:drug effects*; D045744:Cell Line, Tumor; D004305:Dose-Response Relationship, Drug; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology*; D007211:Indoles / Q000494:pharmacology*; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure; D033681:Mitochondrial Membrane Transport Proteins / Q000037:antagonists & inhibitors; D051336:Mitochondrial Membranes / Q000187:drug effects / Q000378:metabolism; D000083162:Mitochondrial Permeability Transition Pore; D009285:Naphthoquinones / Q000494:pharmacology*; D009336:Necrosis / Q000473:pathology*; D010539:Permeability / Q000187:drug effects; D051028:bcl-2-Associated X Protein / Q000378:metabolism
D007093:Imidazoles; D007211:Indoles; D033681:Mitochondrial Membrane Transport Proteins; D000083162:Mitochondrial Permeability Transition Pore; D009285:Naphthoquinones; D051028:bcl-2-Associated X Protein; C507699:necrostatin-1; C016101:shikonin