Altered metabolism is one of the hallmarks of cancer cells. Cell cycling and protein synthesis are both key
physiological tasks for cancer cells. In recent years, interest has been renewed as clear that many of the signaling
pathways that are affected by genetic mutations and the tumor microenvironment have a profound effect on core
metabolism of cancer cells. Metabolic alterations in cancer cells are numerous and include aerobic glycolysis,
reduced oxidative phosphorylation and the increased generation of biosynthetic intermediates needed for cell
growth and proliferation. Furthermore, accelerated protein turnover seen in many cancer patients and whole body
protein turnover is increased with advancing stage of disease. Cancer cells alter their consumption and the way
they process sugars, fats, amino acids and other energy sources to satisfy the demands of continuous proliferation.
The possible effects of specific amino acid, methionine, asparagine, arginine, tyrosine and glutamine, etc. on
protein cancer metabolism are discussed. Evidences confirm a contribution of proteins in all cancer stages and
describe metabolism of protein in cancer and how amino acids can be targeted to management or initially prevent
different types of cancer. Several studies suggest that people who eat more red meat have higher risk for
developing colorectal cancer than those who eat less red meat, but avoiding processed meats is even more
important for cancer prevention. In this review we summarize the role of proteins in cancer etiology, metabolism,
its complication, prevention and treatments.
A Review on Protein and Cancer ; Etiology, Metabolism and Management
1. A Review on Protein and Cancer:
Etiology, Metabolism and Management
By:
Abdel-Rahman Ragab
4th level Student
Zoology Chemistry department
Under Supervision of;Prof Dr : Adel Abdel-Moneim
2. publications
1-Abdel-Moneim A,Ragab A,Magdy A,Mohamed A E,Amged R
(2016):CANCER METABOLISM,Lap Lambert Acaedemic Publishing
,Germany.
2-Adel Abdel-Moneim & Abdel-Rahman Ragab. CANCER PROTEIN
METABOLISM: REVIEW ON ETIOLOGY, PROGRESSION AND
MANAGEMENT. EJBPS 2016, 3 (6), 63-80.
Abdel-Rahman Ragab 2016
6. Introduction
cancer classification
Cancer
classification
According to
site of
origin:
Ex:breast,pr
ostate,lung,
Liver and
brain cancer
According
to behavior
:benign
&malignant
According to
tissue type
(anatomy):
Carcinoma,
Sarcoma,
Lymphoma,
Leukemias,
Myeloma
And Mixed types
According to
grade
(histological
classification):
Grade 1,2,3,4
and 5
According to
clinical
stage:
Stage 0,1,2,3
and 4Abdel-Rahman Ragab 2016
7. Introduction cancer diagnosis
Morphological
methods
Biomarker
genes or
proteins:ex
BRCA1 /
BRCA2
(Breast/Ovaria
n Cancer)
Sampling methods:
(Incisional,Excisional,
Fine needle aspiration) biobsy,Cytology,
Bone marrow aspiration,Endoscopic procedures
Molecular
techniques:
Pcr, FISH, SKI,
DNA microarrays,
Flow
cytometry,EM and
IHC
Imaging
diagnosis:CT,MR
I scan, X-rays,
Mammography,
Nuclear
medicine scans,
Ultrasound
Diagnostic
techniques
Abdel-RahmanRagab 2016
8. Aim of work
The goal of the current review is elucidate the
role of abnormal protein metabolism in cancer
states: etiology, developing, progression, and
cancer complication related to protein
metabolism. Moreover, the treatment and dietary
guidelines for prevention using safe protein
natural products.
Abdel-Rahman Ragab 2016
10. abnormal metabolism
etiological role.
Loss of due to
P53 mutation
Mutation
↓
oncogene
.
glycine N-
methyltransfe
-rase
dysfynction→
hypermethyla
-tion→
activation
Ras →liver
cancer
arginase
dysfunction→
colon cancer
Transglutami-
nase 4
differential
splicing
mRNA→
prostate
cancer
+
↑temp
+
certain
sugar→
acrylamide
Hypermethyl
-ation
suppressor
gene
(mutation)
Methionine: Asparagine Glutamine: Arginine: Glycine: proto-
oncogene
apoptosis
11. Digestion and
absorption in cancer
Mechanical
Digestive
abnormalities
Lack of appetite &
reduced
Food
intake
Cancer
Associated
Weight loss
maldigestion
malabsorption
Patient suffer from:
Dysgeusia,
Early satiation,
Nausea,
Dysphagia,
Odynophagia mucotis,
Constipation,
Diarrhea,
Gastric infiltration and
bowel
12. Protein Metabolism during cancer proliferation
Glutamine
2nd principal nutrient
Oxidn (NADH &FADH2)
Provide N
(pyrines,pyrimidine,nonessential
a.a Import essential a.a
↑c-myc ↓Rb akg→TCA
F.a.a unavailable
extracellular protein lysis
entosis of living cells
phagocytosis of apoptotic
bodies
Arginine 4 N
,precursor proline
Albumin lysis to
F.A.A for N &E
Tryptophan
catabolism
suppress antitumor
immune response
Warburg effect cancer have ↑rate
glucose consumption
reverse Warburg tumor consume
(lactate,ketone bodies,glutamin,F.A to
produce E
increase A.A
consumption→overexpression cell
surface receptor
Metabolism during
cancer
development
14. metastasis
Means: cancer spread from organ to another through b.v. or lymph ex:lung→brain
Metalloproteinases:
degrade the basement membrane.
Fibronectin:
break down (ECM).
Osteopontin (OPN)
Galectin-3
Transforming growth factor-β (TGF-β)
Fibroblast activation protein α
Actin
EMT Type III
Integrins
Mammalian translationally controlled tumor protein
(TCTP)
15. Cachexia
Means: Catabolic process include muscle wasting with or without fat loss and
cannot be fully reversed.
Tumor
inflammation
Cytokine:
IL2,IL6
and TNF-
alpha
Hypothalamus
(appetite
center)
Anorexia
and
Continuous
daily
protein
turn over
↓ plasma anabolic
hormone
Testosterone
GH
Insulin or its
sensitivity of
sk. muscle
proteolytic
pathways
Ex:lysosomal
system
Muscle
apoptosis
cachexia
N.B.Cachexia cause loss of respiratory muscle function will lead to respiratory failure
w lead to death.
16. prevention
Limit Consumption of Processed Meats and Red Meats.
•High intake associated with Colorectal ,colon, rectal and breast cancer
•Minimize consumption of processed meats such as bacon, sausage, luncheon meats
and hot dogs
•choose fish, poultry, or beans as an alternative to red meat
•prepare meat, poultry, and fish by baking,broiling,or poaching rather than by frying or
charboilling
Use Soy Products
•good alternative to meat
•have weak estrogenic activity and may protect against hormone-dependent cancers
•decrease the risk of cancers of the breast ,prostate,or endometrium
Use dairy product
•Higher intakes of milk and total dairy products
•Reduce risk of colon For colorectal cancer and breast cancer
18. Cachexia treatment
Testosterone
Increase
muscle mass by
reducing loss
of sk. Muscle
a.a
Recombinant
GH improve
nutritional
status
Gherlin improve
lean and total
body mass
Insulin
Anabolic to
sk. Muscle
&inhibits
lipolysis
19. conclusion
Tumorigenesis is dependent on the reprogramming of cellular metabolism consequence of oncogenic
mutations. A common feature of cancer cell metabolism is the ability to acquire necessary nutrients
from a frequently nutrient-poor environment and utilize these nutrients to both maintain viability and
build new biomass.
There is clearly a great deal to learned about the interrelation of glucose and glutamine metabolism in
support of cell growth and proliferation, and how nutrient metabolism is coordinated to support
successful cell growth/proliferation.
Therefore, the ultimate goal is to design treatment strategies that affect several proteins metabolism
pathways that slow tumor progression, improve the response to therapy and result in a positive clinical
outcome. Evidences reviewed confirm a contribution of proteins in all cancer stages and describe
metabolism of protein in cancer and how several amino acid can be targeted to management or
initially prevent different types of cancer. Moreover, if we are not able to eradicate cancer in the future
decades, there is still much great effort should be done to prevent cancer occurrence with healthy diet
and change our lifestyle.
20. Acknowledgment
My foremost and greatest gratitude and indebtedness go ALLAH for his guidance and
support in my all life and lightening my path to finish this thesis.
I am sincerely grateful to Prof.Dr.Adel Abdel-Moneim Ahmed ,professor of physiology
,department of zoology ,faculty of science ,beni-suef university for his choice of the review
point ,fruitful direction ,accurate revision of this work ,valuable and constructive
discussion and his kind encouragement and interest through the entire work.
Words will never be able to express my deepest gratitude to my parents, brothers and my
sister whom give me loved and devote all their comfort for me to overcome the hard times.
Last but not least my special and warmest acknowledgment go to my parents whom the
joy of our life and the light of our eyes.
Abdel-Rahman Ragab Qoureny