Abstract
In cancer chemotherapy, it is necessary to design an agent that suppresses or inhibits the targets that influence cell growth and apoptosis. We focus on the apoptotic pathway via mitochondria in this article. In this pathway, c-Jun N-terminal kinase (JNK), one of the stress activated protein kinases, is predominantly activated by apoptotic stimuli. JNK activity is inhibited by the binding of glutathione S-transferase P1-1 (GST P1-1) through protein-protein interactions. It has been noted that GST P1-1 overexpression plays an important role in carcinogenesis and in part in the MDR phenotype. We show several useful modifications of an anticancer agent that suppress the enzyme activity and expression of GST P1-1. The release of cytochrome c from mitochondria to the cytosol during apoptosis is mediated by the mitochondrial permeability transition pore, which is a protein complex formed by the voltage-dependent anion channel, members of the pro- and anti- apoptotic Bax-Bcl-2 protein family, cyclophilin D, and adenine nucleotide (ADP / ATP) translocators. We propose some drugs, including a proteasome inhibitor that can triger the permeability transition.
Keywords: Chemotherapeutic, proteasome, adenine nucleotide, cyclophilin D
Current Cancer Drug Targets
Title: Chemotherapeutic Agents That Induce Mitochondrial Apoptosis
Volume: 4 Issue: 7
Author(s): Tadashi Asakura and Kiyoshi Ohkawa
Affiliation:
Keywords: Chemotherapeutic, proteasome, adenine nucleotide, cyclophilin D
Abstract: In cancer chemotherapy, it is necessary to design an agent that suppresses or inhibits the targets that influence cell growth and apoptosis. We focus on the apoptotic pathway via mitochondria in this article. In this pathway, c-Jun N-terminal kinase (JNK), one of the stress activated protein kinases, is predominantly activated by apoptotic stimuli. JNK activity is inhibited by the binding of glutathione S-transferase P1-1 (GST P1-1) through protein-protein interactions. It has been noted that GST P1-1 overexpression plays an important role in carcinogenesis and in part in the MDR phenotype. We show several useful modifications of an anticancer agent that suppress the enzyme activity and expression of GST P1-1. The release of cytochrome c from mitochondria to the cytosol during apoptosis is mediated by the mitochondrial permeability transition pore, which is a protein complex formed by the voltage-dependent anion channel, members of the pro- and anti- apoptotic Bax-Bcl-2 protein family, cyclophilin D, and adenine nucleotide (ADP / ATP) translocators. We propose some drugs, including a proteasome inhibitor that can triger the permeability transition.
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Cite this article as:
Asakura Tadashi and Ohkawa Kiyoshi, Chemotherapeutic Agents That Induce Mitochondrial Apoptosis, Current Cancer Drug Targets 2004; 4 (7) . https://dx.doi.org/10.2174/1568009043332772
DOI https://dx.doi.org/10.2174/1568009043332772 |
Print ISSN 1568-0096 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-5576 |
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