Cancer

Oxidative Stress and Dietary Antioxidants

Victor R Preedy

• Publisher: Academic Press
• Year: 2014
• ISBN:
  9780124055247
• Topic: Medicine
• Subtopic: Oncology

Cancer: Oxidative Stress and Dietary Antioxidants bridges the trans-disciplinary divide and covers in a single volume the science of oxidative stress in cancer and then the potentially therapeutic usage of natural antioxidants in the diet or food matrix. The processes within the science of oxidative stress are described in concert with other processes such as apoptosis, cell signaling, and receptor mediated responses. This approach recognizes that diseases are often multifactorial and that oxidative stress is a single component of this.

Oncologists, cancer researchers, and nutritionists are separated by divergent skills and professional disciplines that need to be bridged in order to advance preventative as well as treatment strategies. While oncologists and cancer researchers may study the underlying pathogenesis of cancer, they are less likely to be conversant in the science of nutrition and dietetics. On the other hand, nutritionists and dietitians are less conversant with the detailed clinical background and science of oncology. This book addresses this gap and brings each of these disciplines to bear on the processes inherent in the oxidative stress of cancer.

• Nutritionists can apply information related to mitochondrial oxidative stress in one disease to diet-related strategies in another unrelated disease
• Dietitians can prescribe new foods or diets containing anti-oxidants for conditions resistant to conventional pharmacological treatments
• Dietitians, after learning about the basic biology of oxidative stress, will be able to suggest new treatments to their multidisciplinary teams
• Nutritionists and dietitians will gain an understanding of cell signaling, and be able to suggest new preventative or therapeutic strategies with anti-oxidant rich foods

Section 1

Oxidative Stress and Cancer

Outline

Chapter 1. The Role of Oxidative Stress in Breast Cancer

Chapter 2. Oxidative Stress and Prostate Cancer

Chapter 3. Oxidative Stress in Lung Cancer

Chapter 4. Oxidative Stress and Stomach Cancer

Chapter 5. The Role of Oxidative Stress in Ovarian Cancer

Chapter 6. Role of Oxidative Stress in Human Papillomavirus-Driven Cervical Carcinogenesis

Chapter 7. Inflammation and Oxidative DNA Damage

Chapter 1

The Role of Oxidative Stress in Breast Cancer

Gayathri R. Devi, Jennifer L. Allensworth, Myron K. Evans, and Scott J. Sauer Department of Surgery, Division of Surgical Sciences and Duke Cancer Institute, Duke University Medical Center, Durham, NC, USA

Abstract

Breast cancer is the most common cancer in women worldwide and it accounts for the second highest morbidity and mortality. Disease etiology and progression is multifactorial and several risk factors associated with breast cancer exert their effects by modulation of oxidative stress status in the cells. Oxidative stress occurs due to an imbalance between reactive species and antioxidant defenses in the cells. Excess reactive species are deleterious in normal cells, while in cancer cells, they can lead to accelerated growth and survival correlating with an aggressive and therapy-resistant phenotype. Specifically, risk factors and their effect on the oxidative stress response are associated with breast cancer development, progression, and treatment outcome.

This chapter provides a review of the accepted concepts, recent findings, and limitations in the understanding of the cross-talk between antioxidant capacity, redox-sensitive transcription factors, and cell survival/death signaling in oxidative stress response and redox adaptation in breast cancer. Addressing these matters and identifying pathway dysregulation is required for a rational basis to improve the design of redox-related therapeutics and clinical trials in breast cancer.

Keywords

reactive oxygen species; redox adaptation; antioxidants; superoxide dismutase; apoptosis; estrogen; epigenetics; inflammation; aging; hypoxia

List of Abbreviations

8-OHdG	8-Hydroxydeoxyguanosine
γ-GCL	Gamma-glutamylcysteine synthetase
γ-GCS	Gamma-glutathione synthase
Akt	Protein kinase B
AP-1	Activator protein-1
ARE	Antioxidant response element
Bax	Bcl-2-associated X protein
Bcl-2	B-cell lymphoma 2
Bcl-xl	B-cell lymphoma-extra large
BRCA1	Breast cancer susceptibility gene 1
BSO	Buthionine sulfoximine
CA9	Carbonic anhydrase IX
c-Abl	Abelson murine leukemia viral oncogene homolog
CD	Conjugated dienes
cFLIP	Cellular FLICE inhibitory protein
cIAP	Cellular inhibitor of apoptosis
COX2	Cyclo-oxygenase 2
CYP	Cytochrome P450
CYP1B1	CYP family 1, subfamily B, polypeptide 1
CYP1A1/2	CYP family 1, subfamily A, polypeptide 1/2
DNMT	DNA methyltranserase
EGFR	Epidermal growth factor receptor
eNOS	Endothelial nitric oxide synthases
EPO	Erythropoietin
ER	Estrogen receptor
ERE	Estrogen response elements
ERK	Extracellular-signal-regulated kinase
GLUT1	Glucose transporter 1
GPCR	G-protein coupled receptor
GPx	Glutathione peroxidase
GSH	Glutathione
GSK3β	Glycogen synthase kinase 3β
GSR	Glutathione reductase
GSS	Glutathione synthetase
GSSG	Glutathione disulfide
GST	Glutathioine S-transferase
GSTP	Glutathione-S-transferase P1
HDAC1	Histone deacetylase 1
HER2	Human epidermal growth factor receptor 2
HIF-1	Hypoxia inducible factor 1
HO-1	Heme oxygenase 1
HRE	Hypoxia response elements
IGFBP5	Insulin-like growth factor-binding protein 5
IHC	Immunohistochemistry
IKK	IκB Kinase
IL-6	Interleukin-6
iNOS	Inducible nitric oxide synthases
Keap1	Kelch-like ECH-associated protein 1
LDH-A	Lactate dehydrogenase-A
LOH	Loss of heterozygosity
LOOH	Lipid hydroperoxides
MAPK	Mitogen-activated protein kinase
MAPKKK	MAPK kinase kinase
MDA	Malondialdehyde
MMP	Matrix metalloproteinase
mETC	Mitochondrial electron transport chain
NDRG1	N-Myc downstream-regulated 1
NF-κB	Nuclear factor kappa-light-chain-enhancer of activated B cells
nNOS	Neuronal nitric oxide synthases
NOS	Nitric oxide synthases
NQO1	NADH quinone oxidoreductase 1
Nrf2	Nuclear factor (erythroid-derived 2)-like 2
NSAID	Nonsteroidal anti-inflammatory drug
PGE2	Prostaglandin 2
PI3K	Phosphatidylinositide 3-kinase
PR	Progesterone receptor
Prx	Peroxiredoxins
PTEN	Phosphatase and tensin homolog
Ras	Rat sarcoma protein
RNS	Reactive nitrogen species
ROS	Reactive oxygen species
RTK	Receptor tyrosine kinase
SERM	Selective estrogen receptor modulator
siRNA	Small interfering RNA
Smac(Diablo)	Second mitochondria-derived activator of caspases
SOD	Superoxide dismutase
Src	Sarcoma protein
TAK1	Transforming growth factor-β activated kinase-1
tBHQ	tert-Butylhydroquinone
TERT	Telomerase reverse transcriptase protein
TNBC	Triple negative breast cancer
TNFα	Tumor necrosis factor α
TRAF	TNF receptor associated factor
TRAIL	TNF-related apoptosis-inducing ligand
Trx	Thioredoxins
VEGF	Vascular endothelial growth factor
XIAP	X-linked inhibitor of apoptosis protein

Introduction

Redox Homeostasis: ROS Production and Elimination

Reactive species, also termed oxidants, are byproducts of key aerobic cellular processes of respiration, metabolism, and the mitochondrial electron transport chain (mETC),^1,2 and are removed continuously by an array of antioxidant mechanisms. These species include reactive oxygen species (ROS) and reactive nitrogen species (RNS). ROS are mainly comprised of neutral molecules (H₂O₂), radicals (hydroxyl radicals), and ions (superoxide).³ On the other hand, nitric oxide, the main form of RNS in the cell, is produced by a family of enzymes (nitric oxide synthases, NOSs) that include iNOS (inducible), eNOS (endothelial), and nNOS (neuronal).⁴ ROS can also be produced at somewhat low levels in response to the activation of certain signaling pathways, such as the epidermal growth factor receptor (EGFR) pathway.⁵ Activation of these pathways has been shown to be important for proliferation, as well as the oncogenic and metastatic potential of cancer cells. Extracellular sources of ROS include tobacco, smoke, drugs, xenobiotics, radiation, and high levels of heat, most of which either activate a stress response or directly damage cellular components leading to ROS production.⁶

Cells have natural...

Table of contents

• Cover image
• Title page
• Table of Contents
• Copyright
• Preface
• List of Contributors
• Section 1 Oxidative Stress and Cancer
• Section 2 Antioxidants and Cancer
• Index
• Color Plates