Transcript Biochemistry of Carcinogenesis

King Saud University
College of Science
Disclaimer
Department of
Biochemistry
The texts, tables and images contained in this course presentation
are not my own, they can be found on:
– References supplied
– Atlases or
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BCH 475
Biochemistry of Carcinogenesis
Professor A. S. Alhomida
Summer, 2008
Part 4
1
2
Eating to Prevent Cancer
How a Healthy Diet and
Physical Activity May Help
Keep You Cancer-Free
3
The Relationship Between
Lifestyle and cancer
A total of 60-70% of cancers may be
lifestyle related!
30-40% of cancers can be prevented by a
healthy diet, healthy weight, and regular
physical activity
30% of cancers can be prevented by not
using tobacco
4
The Relationship Between
Lifestyle and cancer
Many foods and nutrients have been
linked to cancer prevention
For cancer prevention, focus on an overall
healthy diet rather than specific foods or
nutrients
Maintain a healthy weight throughout life
5
The Relationship Between
Lifestyle and cancer
Adopt a physically active lifestyle
Eat a variety of foods, with an emphasis
on plant sources
Limit consumption of alcoholic beverages
6
Maintain a Healthy Weight
Being overweight and inactive accounts
for 1/3 of the worldwide cases of breast,
colon, endometrial, kidney, and
espophageal cancers
Balance calorie intake with physical
activity
7
Maintain a Healthy Weight
Avoid excessive weight gain throughout
life
Achieve and maintain a healthy weight if
currently overweight or obese
8
Body Mass Index (BMI)
Body mass index is defined as the
individual's body weight divided by the
square of their height
BMI provides a reliable indicator of body
fatness for most people and is used to
screen for weight categories that may lead
to health problems
9
Body Mass Index (BMI)
It was invented between 1830 and 1850
by the Belgian polymath Adolphe Quetelet
during the course of developing "social
physics"
The formulas universally used in medicine
produce a unit of measure of kg/m2
Body mass index may be accurately
calculated using the formulas below:
10
Maintain a Healthy Weight
Body Mass Index (BMI)
weight ( kg)
BMI 
2
2
height (m )
11
Maintain a Healthy Weight
Know your Body Mass Index (BMI)
Below 18.5
18.5 – 24.9
25.0 – 29.9
30.0 and Above
Underweight
Normal weight
Overweight
Obese
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Tips for Maintaining a Healthy
Weight
Eat plenty of fruits and vegetables
Limit simple sugars (cakes, cookies, pies,
candies, sweetened drinks)
Eat smaller portions of everything
Add physical activity to your life
13
Adopt a Physically Active
Lifestyle
Adults:
– Get at least 30 minutes or more moderate to
vigorous physical activity five or more days of
the week, 45-60 minutes if possible
Children and adolescents:
– Get 60 minutes per day of moderate to
vigorous physical activity at least five days per
week
14
Healthy Foods
Eat a variety of healthy foods with an
emphasis on plant foods
Plant foods (fruits, vegetables, whole
grains, and legumes) are packed with
vitamins, minerals, antioxidants, and other
substances that work together to lower
risks of several cancers
15
Cancers Associated with Low
Intake of Plant Foods
Lung cancer
Mouth cancer
Stomach cancer
Colon cancer
16
Healthy Foods
Eat five or more servings of fruits and
vegetables each day
Choose whole grains over processed
(refined) grains and sugars
Limit consumption of processed red meats
17
Healthy Foods
Fruits and vegetables are rich in fiber,
vitamins, minerals, and phytochemicals
Whole grains are rich in fiber, vitamins,
minerals, and phytochemicals
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Healthy Foods
They contain several substances that have
been linked to lower cancer risk including
fiber, antioxidants, phenols, lignans,
polyestrogens, and saponins
Standard serving sizes:
– One cup raw fruit or vegetable, ½ cup canned
fruit or cooked vegetable, one medium piece
of fruit, ¼ cup dried fruit
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Fruits and Vegetables
Choose five or more servings of fruits and
vegetables each day
Choose colorful fruits and vegetables for
the most nutrient content
Choose a variety of fruits and vegetables
Enjoy fruits and vegetables prepared and
served without added fat or sugar
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Fruits and Vegetables
One serving equals:
– ½ cup cooked vegetables
– One cup leafy vegetables
– ½ cup 100% juice
– One medium piece of fruit
– ½ cup fresh, frozen, or canned fruit, or ¼ cup
dried fruit
21
Cancers Associated with
Alcohol Intake
Oral (mouth)
Pharyngeal (throat)
Esophageal
Laryngeal (voice box)
Breast
Liver
– Use of tobacco at the same time as alcohol
increases your risk for developing these
cancers
22
Dietary Factors Associated with
Reduced Cancer Risk
Dietary fiber
– Colorectal, pancreas, breast
Folic acid
– Cervix, colorectal
Vitamin D and calcium
– Colorectal, breast
23
Dietary Factors Associated with
Reduced Cancer Risk
Vitamin C from foods
– Oral cavity, esophagus, lung, stomach,
pancreas, cervix
Tea (flavonoids)
Lung, colorectal
α-tocopherol
Lung
Soy isoflavones?
Breast
24
Dietary Factors Associated with
Reduced Cancer Risk
Antioxidants (nutrient and non-nutrient)
from foods
– Colorectal, lung, breast, cervix, prostate,
esophagus, stomach
25
Food Components that May
Prevent Cancer
Antioxidants
– Vitamins A, C, E, cartenoids, selenium
– There is no evidence to support taking
antioxidant supplements to prevent cancer
Dietary fiber
– The link between fiber and cancer is weak
– Foods that contain fiber are high in other
nutrients that may prevent cancer
26
Food Components that May
Prevent Cancer
Phytochemicals
– Compounds made by plants that may prevent
cancer (e.g., lycopene in tomato)
– There is no evidence that phytochemical
supplements prevent cancer
– Lycopene is a phytochemical (red-orange
carotene pigment found in tomatoes and other
pink and red fruits and vegetables)
27
Food Components that May
Prevent Cancer
Phytochemicals
– Several studies report that consuming tomato
products reduces the risk of some cancers but
the link with lycopene is uncertain
– This has been highly touted as preventing
prostate cancer based on one study
– Further studies are in process
28
Food Components that May
Prevent Cancer
Vitamin D
– There is growing evidence that vitamin D may
help prevent colon, prostate, and breast
cancer
– In some cases supplements are
recommended
29
Food Components that May
Prevent Cancer
Vitamin D
– Research is needed to determine how much
vitamin D is needed by different populations,
but it appears to current Dietary Reference
Intakes’ (DRI) may be inadequate to prevent
cancer
– A balanced diet, moderate supplementation,
and frequent sun exposure (small amounts)
are preferred method to obtain Vitamin D
30
Do These Foods Prevent
Cancer?
Cruceriferous vegetables (broccoli,
cauliflower, cabbage)
These vegetables may contain
phytochemicals that reduce cancer risk
Eat a wide variety of vegetables, not just
cruceriferous vegetables
31
Cruceriferous Vegetables
32
Cruceriferous Vegetables
33
Do These Foods Prevent
Cancer?
Soy foods
– Contain phytochemicals that may fight cancer
(based on animal studies)
– Soy supplements should not be taken to
reduce cancer risk
– Women with breast cancer should consume
only moderate amounts of soy
High doses of soy could increase the risk of
estrogen-responsive cancers, such as breast or
endrometrial cancer
34
Do These Foods Prevent
Cancer?
Tea
– Some research (animal studies) suggests that
tea may have antioxidant properties and
prevent cancer
– Studies in humans have been less conclusive
35
Do These Foods Prevent
Cancer?
Garlic
– The health benefits of garlic have been widely
publicized
– There is not enough evidence to support
garlic as a food to prevent cancer at this time
36
Things That Don’t Cause
Cancer
Food additives
Irridiated foods
Bioengineered foods
Aspartame
Coffee
Dietary fat
Pesticides and herbicides (wash
thoroughly)
37
Things That Don’t Cause
Cancer
Based on information provided by the
American Cancer Society, there is not
evidence to tie any of these items with
cancer
The low doses of pesticides and
herbicides in food do not appear to
increase the risk of cancer
38
Dietary Factors Inversely
Related to Cancer Risk
Alcohol
– Mouth, pharnyx, larnyx, esophagus, liverconvincing
– Breast, colon, rectum- probable
Salt
– Stomach- probable
Sucrose
– Colon, rectum
39
Dietary Factors Inversely
Related to Cancer Risk
Meat (especially charbroiled)
– Colon and rectum- probable
Total and saturated fat
– Lung, colon, rectum, breast, prostatepossible
40
Chemopreventive Non-nutritive
Dietary Factors
Compound
Food Source
Cinnamic acid
Fruit, vegetables, coffee beans
Flavonoids (catechins,
quercitin, isoflavones,
anthocyanins)
vegetables, fruit, citrus fruit, celery,
parsley,onions, grains, tea, soybean
Indoles
Cruciferous vegetables
Isothiocyanates
Cruciferous vegetables
Lignans
Whole grains, flax
Organosulfur
Garlic, Onion
Terpenes
Citrus, spices
41
Role of Dietary Factors in
Carcinogenesis
Exposure to
Carcinogen
Inhibitors of Activation
DNA Binding
Blocking Agents
Reaction with Cellular Targets
DNA Damage, Mutagenesis
Suppressing Agents
Neoplastic
Manifestation
42
Inhibitors of Activation
Inducers of Phase I Biotransformation
Enzymes
– Cytochrome P450 mono-oxygenase system
– Converts hydrophobic to hydrophilic
compounds for elimination by forming reactive
intermediate
43
Phase I Activation and Phase II
Detoxification Reactions
Bioactivation
Carcinogen
Phase I
Detoxification
Primary
Metabolite Phase II
Reactive Intermediate
Secondary
Metabolite
Excretion
Covalent Binding
Acute Cellular
Injury
Delayed
Toxicity
Mutations &
Cancer
44
Blocking Agents
Inducers of phase II detoxification
Enzymes
– Glutathione S-transferases, sulfotransferases,
UDP-gluronosyltransferases
– Phenols, isothiocyanates, flavones, and
coumarins
– Affect gene expression at transcriptional level
Binders of free radical intermediates
– Antioxidants
45
Suppressing Agents
Inhibit development of cancer subsequent
to administration of carcinogen
– Retinoids and carotenoids
– Protease inhibitors
– Phenols and polyphenols
– Selenium
Antioxidant protection
46
Role of Antioxidants in
Carcinogenesis
Normal cell
Reactive O2
+
O2-Derived
Free Radicals
Lipid peroxidation
in cell membranes
Antioxidant
Oxidized bases
Scavengers &
in DNA
Enzyme Systems
Cell repair
Exposure of DNA
Cell Death
Lipid Peroxides
Mutations
DNA Repair
Normal Cell
Compensatory
Cellular
Hypoproliferation
Cell Death
No Repair
Less regulation of cell
growth & differentiation
Cell Hyperproliferation
Exposure of DNA
Further Mutations47
Antioxidant Protection
Cellular
Antioxidants
Enzyme Systems
Minerals
Catalase
Peroxidase
Fe
Glutathione
Peroxidase
Se, AA
Scavengers
Vitamins
Superoxide
Dismutase
Cu/Mn
Membrane
Lipid
Protection
Aqueous
Comptmts
E
C
CoQ10
Polyphenols
Isothiocyanates
Non-nutrient
Plant Chemicals
Lipid
Comptmts
Carotenoids
Other Protective Effects: Folic
Acid
Thymidine synthesis inhibited
Lack of methyl donor from methylene-THF
or S-adenosyl-methionine
DNA hypomethylation
Uracil misincorporation
DNA repair by excision
Increase in fragile sites and chromosomal
breaks
49
Folate Deficiency and DNA
Stability
CH3
X
DNA
TMP
dUMP
U
Chromosomal
damage
double
strand
break
single
strand
break
A
DNA repair removes
misincorporated
uracil
50
Moderators of Insulin Sensitivity
and Resistance
Moderators of insulin and insulin-like
growth factor (IGF-1)
– IGF-1 protects against apoptosis
– Insulin and IGF-1 increase aberrant crypt foci
growth
Precursor of colorectal tumors
– Insulin resistance associated with increased
tumor promotion in animal models (r = 0.67)
51
Insulin Resistance and Relative
Risk of Colon Cancer
Dietary Glycemic Index
Physical
Activity
Low
Medium
High
High
1.0
1.3
1.4
Medium
1.6
1.8
2.1
Low
1.5
1.9
3.5
52
Other Protective Effects
Inhibitors of invasive processes
– Stimulate plasminogen activator inhibitors
Reduces plasmin-stimulated degradation of
extracellular membrane
Dietary fiber, low glycemic index sugars
53