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Full-Text Articles in Biochemistry, Biophysics, and Structural Biology
Patterns Of Apoptotic Poly(Adp-Ribose) Polymerase Cleavage Induced By Laromustine And Its Analogs, Adam N. Paine
Patterns Of Apoptotic Poly(Adp-Ribose) Polymerase Cleavage Induced By Laromustine And Its Analogs, Adam N. Paine
Honors Theses
The anticancer prodrug Laromustine (VNP40101M) has produced promising remission rates in clinical trials among leukemic patients relative to currently available chemotherapeutics. Such improvements demand that the agent’s mechanism of action be elucidated. This study aimed to determine the role of poly(ADP-ribose) polymerase (PARP) in Laromustine-induced cell death. Previous studies indicated that the methyl isocyanate produced upon activation of Laromustine is largely responsible for its effective induction of apoptosis. Results reported herein strongly support the activation of a PARP-dependent apoptotic pathway by Laromustine’s carbamoylating and chlorethylating subspecies. Furthermore, it is evident that the Laromustine-induced PARP-dependent apoptosis is primarily attributable to methyl …