Cytochrome c is rapidly extruded from apoptotic cells and detectable in serum of anticancer-drug treated tumor patients.

Abstract

Two major forms of cell death, necrosis and apoptosis, exist. Apoptosis, also known as programmed cell death (PCD), is the form of cell death that commonly occurs in development and many pathophysiological situations1,2. In contrast, necrosis is a more passive process that occurs when cells have been severely damaged by noxious insults. Apoptosis is triggered by two major signaling pathways that are either controlled by death receptors or mitochondria. In the mitochondrial pathway the initial and crucial event is the release of cytochrome c (Cc) from mitochondria into the cytosol, which can be triggered by diverse apoptotic stimuli including anticancer drugs. Cytosolic Cc together with dATP binds to the apoptosis regulator Apaf-13,4thus leading to the formation of the apoptosome and the initiation of the proteolytic death cascade. Antiapoptotic Bc1-2 family members suppress Cc release3,4whereas proapototic members such as Bax promote its liberation5,6. However, the exact mechanism of Cc release remains unknown.