A Review on Protein and Cancer:Etiology, Metabolism and Management
By:Abdel-Rahman Ragab4th level StudentZoology Chemistry department
Under Supervision of;Prof Dr : Adel Abdel-Moneim
publications1-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
contents
1-Introduction.2-Abnormal metabolism etiological role.3-Abnormal metabolism during cancer development.4-Complications of cancer.5-Prevention and treatment of cancer.6-Conclusion.
Abdel-Rahman Ragab 2016
Introductioncancer classification
Cancer classification
According to site of origin:Ex:breast,pros
tate,lung,Liver and
brain cancer
According to behavior :be
nign &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
Introduction cancer diagnosis
Morphological methods
Biomarkergenes or
proteins:ex BRCA1 / BRCA2 (Breast/Ovarian
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,MRI
scan, X-rays, Mammography,
Nuclear medicine scans, Ultrasound
Diagnostic techniques
Abdel-Rahman Ragab 2016
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
Protein metabolism in normal cells
abnormal metabolism etiological role.
Loss of due to P53 mutation
Mutation ↓
oncogene.
glycine N-methyltransfe-rase dysfynction→hyperm
ethyla-tion→
activation Ras →liver
cancer
arginase dysfuncti
on→colon cancer
Transglutami-nase 4 differential splicing
mRNA→prostate cancer
+↑temp
+certain
sugar→acrylamid
e
Hypermethyl-ation
suppressor gene
(mutation)
Methionine: Asparagine Glutamine: Arginine: Glycine: proto-oncogene
apoptosis
Digestion and absorption in cancer
Mechanical Digestive
abnormalities
Lack of appetite & reduced
Foodintake
Cancer Associated Weight lossmaldigestion
malabsorption
Patient suffer from:Dysgeusia,
Early satiation,Nausea,
Dysphagia,Odynophagia mucotis,
Constipation,Diarrhea,
Gastric infiltration and bowel
Protein Metabolism during cancer proliferationGlutamine
2nd principal nutrientOxidn (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
cellsphagocytosis 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
Cancer complicationInclude:pain,fatigue,difficulty breathing,nausea,diarrhea,constipation,nervous system problem,systemic disorder,angiogenesis,metastasis and cachexia.
metastasisMeans: 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
ActinEMT Type III
IntegrinsMammalian translationally controlled tumor protein (TCTP)
CachexiaMeans: 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 andContinuous daily protein turn over
↓ plasma anabolic hormone
Testosterone GHInsulin 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.
preventionLimit 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
treatment
drug mechanism targetnutlin Inhibit p53-MDM2 interaction p53
azaserine Used for side effects of cancerchemotherapy
Glutamine
Clinical trials --------------------------------------- a.a metabolic enzyme
gefitinib Interfere with a specific molecular target ex: ErbB1
(EGFR)
Tyrosine kinases agents
Cachexia treatment
TestosteroneIncrease
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
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.
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