Apoptosis as a mechanism of cell death by anticancer agents

The molecular targets for most anticancer agents are well known. Although most agents do not produce DNA breaks directly, many induce DNA breaks in cells well in advance of loss of membrane integrity. Electrophoresis of the DNA from cells damaged by cisplatin and a variety of cytotoxic agents demonstrated that internucleosomal DNA digestion occurred as one of the earliest changes within cells destined to die. Later cellular events included cell shrinkage, the formation of blebs and eventual loss of membrane integrity. These observations are consistent with cell death occurring by apoptosis, where internucleosomal DNA digestion is produced by activation of an endogenous endonuclease that is thought to mediate cell death. The prevailing theories of apoptosis states that cell death is initiated by increased cytosolic Ca;Treatment of CHO cells with Ca...