Manipulation of the Cellular Redox State: Effects of Antioxidants on TRAIL-induced Apoptosis in Rhabdomyosarcoma Cells
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Authors
Wagner, Jessie J.
Issue Date
2004
Type
Thesis
Language
en_US
Keywords
Alternative Title
Abstract
Cancer is characterized by the dysfunction of numerous proteins associated with
the regulation of cell growth, leading to uncontrolled proliferation. Therefore, the
selective induction of cell death in transformed (cancerous) cells represents a suitable
therapeutic goal. TRAIL, is a unique member of the TNF superfamily of death ligands,
as it only targets transformed cells for apoptosis. Upon TRAIL ligand-receptor
interaction, procaspase-8 and Fas-associated death domain (FADD) are recruited to the
receptor, forming the death inducing signaling complex (DISC) leading to propagation of
the death signal and a caspase cascade.
By analogy with other family members, this study sought to determine the role of
reactive oxygen species (ROS) in the induction of apoptosis. The antioxidants catalase
(CAT) and glutathione (GSH) were used to induce a reduced environment in the
transformed rhabdomyosarcoma cell line RD, as determined by the quantification of
cellular hydrogen peroxide levels through a DCFH-DA assay. Levels of apoptosis were
assessed through quantification of subdiploid cells in a DNA cell cycle analysis by flow
cytometry. It was found that the induction of a reduced cellular environment by pretreatment with antioxidants sensitized the RD cell line and enhanced TRAIL-induced
apoptosis in these transformed cells. Furthermore, the activity of pro-apoptotic proteins
associated with TRAIL-induced apoptosis increased, and the activity of anti-apoptotic
proteins decreased when cells were treated with the combination of an antioxidant and
TRAIL, but not affected when treated with either agent alone. The results of this study
implicate a combination treatment of TRAIL with antioxidants as a potential therapeutic
option for cancer treatment.
Description
v, 37 p.
Citation
Publisher
Kalamazoo College
License
U.S. copyright laws protect this material. Commercial use or distribution of this material is not permitted without prior written permission of the copyright holder.