Patterns of Apoptotic Poly(ADP-ribose) Polymerase Cleavage Induced by Laromustine and its Analogs
Date of Award
Honors Thesis (Open Access)
Colby College. Chemistry Dept.
Kevin P. Rice
Julie T. Millard
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 isocyanate. As PARP has been implicated in numerous apoptotic pathways, these results advance the ongoing characterization of Laromustine’s cellular death mechanism and begin the process of sequencing apoptotic events.
anticancer, laromustine(VNP40101M), leukemic patients, poly(ADP - ribose), polymerase(PARP), Laromustine, methyl isocyanate, laromustine
Recommended CitationPaine, Adam N., "Patterns of Apoptotic Poly(ADP-ribose) Polymerase Cleavage Induced by Laromustine and its Analogs" (2010). Honors Theses. Paper 603.
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