a review on protein and cancer ; etiology, metabolism and management

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.


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


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.


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

a review on protein and cancer ; etiology, metabolism and management

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