The Biochemical Response of Acetyl Cholinesterasein Prostate Cancer in relation to the Environment

 

Jaleel Ibrahim Asaad¹, Ayad M. J. Al-Mamoori², Hussein Mahmood Shukri³,

Asmaa Ibrahim Sail¹, Enas Shehab Ahmed¹, Aya Nadhmi⁴

¹Biotechnology Research Center, AL-Nahrin University, Iraq

²Biology Dept., College of Science , University of Babylon, Iraq

³Biotechnology College, AL-Nahrin University, Iraq

⁴Biochemistry Departments, Ottawa University, Canada

 

ABSTRACT:

Acetylcholinesterase (ACHE) is an enzyme. Its main extracellular function isto hydrolyze the Acetylcholine to choline and acetate,and maintain the correct levels of Acetylcholine in the body and according to the Environmental Factors. Another function for (ACHE) in intra cellular compartment is to stimulate cell proliferation and apoptosis. In this study, we try to investigate the (ACHE) and prostate cancer overlapping to get new diagnostic markerand/or treatment for prostate cancer. Results: There is no significant difference in serum (ACHE) of patients with prostate cancer (12.90 ± 4.17ng /ml), in comparison to control group (9.0 ± 1.78 ng /ml),(p>0.05). But there is significant increase in serum (ACHE) incases with high grade prostate cancer with Gleason grade more than 7,(11.90 ± 2.11ng /ml),in comparison to lower grade prostate cancerwith Gleason grade less than 7, and control group (10.20 ± 2.20and 9.0 ± 1.78ng /ml respectively),(p<0.05). Conclusion: Because of thevariation inthe level of serum (ACHE) in patients with prostate cancer, this marker can't consider as prognostic protein for diagnosis ofprostate cancer. However further prospective studies are recommended to demonstrate its role in the diagnosis, grading and elimination of the tumor.

 

 

 

INTRODUCTION:

Acetylcholinesterase (ACHE), is an enzyme responsible for hydrolyzing acetylcholine (ACH), the cholinergic neurotransmitter,to choline and acetate.[1]In the human the gene-encoding ACHE is located at chromosome (7q22).[2] There are three isoforms of ACHE. ACHE-synaptic (S) isoform expressed in brain andmuscle tissue. ACHE-erythrocyte (E) isoform is prevalent in the human erythrocytes and ACHE-read-through (R) relatedto stress. There are many non-classical function of ACHE likeneurodegeneration, which are related to Alzheimer’s disease, apoptotic sensitivity, cellular proliferation, anddifferentiation, suggesting a possible role of cholinesterase intumorigenesis.

 

There isStructural alteration of ACHE or abnormal expression and multiple activities have been found in different types of tumors, like brain, lung, ovarian, breast, hepatocellular,renal and colon cancers, which indicate implicating of ACHE in regulating tumor development.[3]. ACHE-R is involved in cell Proliferation,viaformation of apoptosome by affecting the interaction between apoptotic protease-activating factor-1 (Apaf-1) and cytochrome c, then triggers cleavage of procaspase -9 to its active form whereas ACHE-S is involved in apoptosis.[4] Intracellular calcium concentration play important role in ACHE regulation during apoptosis through calcium ionophore (receptors) whichcan elevate ACHE expression at mRNA and protein levels. Calcium chelator suppresses ACHE expression.[5] AChE associated with stress responses due to inflammation.[6,7]

 

MATERIAL AND METHODS:

1-Blood samples were collected by vein puncture from ten patients,newly diagnosed with prostate cancer,in AL-AMAL general hospital in Baghdad – Iraq, and ten blood samplesfrom age matched healthy subjects (control group).

 

2- The agerange is (60-75 year), for patients with PCa and control.

 

3- Blood samples were centrifuged (2000 rpm for 10minutes), the serum immediately stored in -20 C° until analysis

 

4-Then Quantitative Sandwich ELISA technique was used for measuring Acetyl cholinesterase concentrations according to manufacturing company (Elabscience Biotechnology Co., Ltd. China.).

 

Statistical analysis:

SPSS version 17 software (USA) used to analyze the results for comparison between patient and control groups to show the significance differences (P<0.05)

 

RESULTS:

Results reveal no significant difference (p>0.05) in serum acetylcholinesterase (ACHE) inpatients with prostate cancer(12.90 ± 4.17ng /ml),in comparison to control group (9.0 ± 1.78 ng/ml). (Table -1)

 

Table-1 serumacetyl cholinesterase inpatients withprostate cancer and control group (Mean ± SD)

Study Groups	No.	Serum ACHE ng/ml
Patients with prostate cancer (Mean ± SD)	10	12.90 ± 4.17 a
Control group (Mean ± SD)	10	9.0 ± 1.78 a

(P < 0.05,)

 

There is significant increase inserum acetyl cholinesterase (ACHE) in patients withhigh grade prostate cancer (Gleason score more than 7), thanthat of control subjects (11.90 ± 2.11, 9.0 ± 1.78 ng /ml).(p<0.05). (Table -1)

 

There issignificant difference (p<0.05) in serum (ACHE) of patients with high grade prostate cancer (Gleason score more than 7), comparing tothat of patients with lower grade prostate cancer (Gleason score less than 7),(Table1)

 

There is no significant difference (p> 0.05) in serum acetyl cholinesterase of patients with lower grade prostate cancer (Gleason score less than 7), comparing to that of control subjects (10.20 ± 2.20 and 9.0 ± 1.87 ng /mlrespectively).(Table 2)

 

 

Table-2 :Serum Cholinesterase level in patients with prostate cancer withdifferent Gleason score and in controlgroup (Mean± SD)

Study Groups	No.	Serum ACHE ng/ml
Patients with high grade prostate cancer (Gleason score more than 7)	4	11.90 ± 2.11 b
Patients with lower grade prostate cancer (Gleason score less than 7)	6	10.20 ± 2.20 a
Control group (Mean ± SD)	10	9.0 ± 1.78 a

b=(P < 0.05)

 

DISCUSSION:

Serum Acetylcholinesteras levels differs as a result of different types of tumor.Syed and coworkers (2008),mentioned that ACHEhas dual role in colon cancer it has protective role in early stages and in late stage support the progression of the tumor.In patient with prostate cancerthere is no difference in ACHE level from that in normal subjects. [8] Ongane and coworkers (2006) show that ACHE can potentiate the metastasis in breast cancer while Xi H-J and coworkers (2015) refer to the protective effect of high ACHElevel fromlung cancer.[9, 3]

 

This study revealed thatserum ACHE in patients prostate cancer is higher thanthat of healthy subjects, but statistically the difference is not significant, and this result agrees withthat of Syed and coworkers.[8] Anda higher level of serum ACHEin patients with high grade prostate cancer (Gleason score more than 7) than its level in patients with lower grade prostate cancer (Gleason score less than 7) and control group.These resultsrevealed that ACHE promote cellular proliferation inprostate cancer tissue [10], and there is positive relationship betweenserum ACHE levels and Gleason score. Also the level of ACHE in prostate cancer,is not dominant feature may be due to the change in the pattern of ACHE molecules,[11]or through influences of cholinesteraseACHE in tumorigenesis via alteration of cholinesterase gene structure oraberrant in expression of their products in different types of tumor.[12]

 

REFERENCE:

1.     Silman, I and Sussman JL.(2005) Acetylcholinesterase: “Classical” and “non-classical” functions and pharmacology. Curr Opin Pharmacol , 5: 293–302

2.     Getman, DK.; Eubanks ,JH.; Camp, S.; Evans ,GAand Taylor P.(1992) The human gene encoding acetylcholinesterase is located on the long arm of chromosome 7. Am J Hum Genet , 51: 170–7.

3.     Xi, H-J.; Wu, R-P.; Liu, J-J.; Zhang, L-J and Li, Z-S.(2015) Role of acetylcholinesterase in lung cancer Thoracic Cancer. 6, 390–398

4.     Park, SE.; Kim,ND and Yoo, YH (2004) Acetylcholinesterase plays a pivotal role in apoptosome formation. Cancer Res ,64: 2652–2655.

5.     Zhu, H.; Gao, W.; Jiang, H.;Wu, J.; Shi, YFand Zhang, XJ(2007). Calcineurin mediates acetylcholinesterase expression during calcium ionophore A23187-induced HeLa cell apoptosis. Biochim Biophys Acta , 1773: 593–602

6.     Pick, M.;Perry, C.;Lapidot, T(2006) Stress-induced cholinergic Signaling promotes inflammation-associated thrombopoiesis. Blood , 107: 3397–406.

7.     Shaked, I.; Meerson, A and Wolf, Y (2009) Micro RNA-132 potentiates cholinergic anti-inflammatory signaling by targeting acetylcholinesterase. Immunity , 31: 965–973.

8.     Syed, M.; Fenoglio-Preiser ,C.; Skau , K. A.; Weber ,G.F. (2008) Acetylcholinesterase supports anchorage independence in colon cancer Clin Exp Metastasis 25:787–798.

9.     Onganr, P. U..; Mustafa, B.A.; Djamgoz, A.; Whyte, K.; Greenfield, S. A (2006). An acetylcholinesterase-derived peptide inhibits endocytic membrane activity in a human metastatic breast cancer cell line. Biochimica et Biophysica Acta 1760: 415–420

10.   Rayford, W.;Noble, M.J.;Austenfeld, M.A.; J., Weigl, W.K.; Mebust, G.V. ( 1997) Muscarinic cholinergic receptors promote growth of human prostate cancer cells. Prostate,30: 160–166.

11.   Nieto-Ceróna, S.; Vargas-Lópeza, H.; Pérez-Albaceteb, M.; Tovar-Zap,ataa, I.; Martínez-Hernándeza, P.; Rodríguez-Lópezc, J.; Cabezas-Herreraa, J(2010) Analysis of cholinesterases in human prostate and sperm Implications in cancer and fertility. Chemico-Biological Interactions, 187: 432–435

12.   Battisti, V.; Bagatini ,M. D.; Maders, L.;Chiesa, J.; Santos, K.; Gonc¸alves, J.; Abdalla, F.; Battisti, I.;Schetinge, M.; Morsch, V (2012) Cholinesterase activities and biochemical determinations in patients with prostate cancer: Influence of Gleason score, treatment and bone metastasis. Biomedicine and Pharmacotherapy, 66:249–255

 

 

 

 

 

 

Accepted on 21.05.2018          © RJPT All right reserved

Research J. Pharm. and Tech 2018; 11(9): 3897-3899.