The Significance of Poly-Targeting in Apoptosis Induction by Alkylating Agents and Platinum Drugs

摘要: Apoptosis is believed to be an important aspect of the anticancer potency alkylating agents (AAs) and platinum (Pt) complexes. Despite high clinical utility these classes drugs, nature determinants apoptotic sensitivity/resistance cancer cells are not completely understood. One underappreciated wide variable spectrum cellular targets AAs Pt drugs complexity responses poly-targeted insults. This chapter discusses heterogeneity targeting profiles for diverse drug types interdependence routes elicited by damage various targets. Although many target DNA, DNA only cause their effects. Drugs that alkylate proteins strongly apoptotic, even if they do react with DNA. The ability inactivate specific globally distort state proteome needs considered as a self-standing stimulus factor enhances lethal damage. Particular emphasis placed on significance effects redox-regulating thioredoxin family. Disruption protein redox homeostasis likely critical death/survival in response drugs. Differential distortion regulation suggested molecular basis underlying demonstrated potential such irofulven oxaliplatin promote apoptosis while sparing normal cells.