|Year : 2017 | Volume
| Issue : 2 | Page : 367-370
Serum butyrylcholinesterase and zinc in breast cancer
Rupesh Kumar1, Sairoz Razab1, Krishnananda Prabhu1, Satadru Ray2, Bhanu Prakash3
1 Department of Biochemistry, Kasturba Medical College Manipal, Manipal University, Manipal, Karnataka, India
2 Department of Surgical Oncology, Kasturba Medical College Manipal, Manipal University, Manipal, Karnataka, India
3 Department of Radio Therapy, Kasturba Medical College Manipal, Manipal University, Manipal, Karnataka, India
|Date of Web Publication||23-Jun-2017|
Professor and Head, Department of Biochemistry, Kasturba Medical College Manipal, Manipal University, Manipal, Karnataka
Source of Support: None, Conflict of Interest: None
Context: Even though, a large number of serological, molecular markers have been proposed for breast cancer screening, most of them lack specificity, sensitivity, prognostic value, and cost effectiveness. Butyrylcholinesterase (BChE) and its genes are aberrantly expressed in a variety of human cancers. It has-been linked to tumorigenesis, cell proliferation, and cell differentiation. Zinc (Zn) is a cofactor for superoxide dismutase, an enzyme that protects cellular components against free radical-induced damage and carcinogenesis. Therefore, the aim of present study was to estimate and compare serum BChE and serum Zn levels in healthy controls and biopsy proven breast cancer patients before definitive therapy.
Aims: To estimate and compare serum BChE and serum Zn levels in healthy controls and biopsy proven breast cancer patients before definitive therapy.
Settings and Design: Serum BChE and Zn were estimated in 46 newly diagnosed (preoperative) female patients with breast cancer and 50 healthy female volunteers.
Subjects and Methods: Serum BChE and Zn were estimated by spectrophotometric method.
Statistical Analysis Used: Data was expressed as median and inter quartile range. Comparisons between different stages of cancer were done using Kruskal–Wallis test.
Results: There was a significant increase in serum BChE and Zn in breast cancer patients compared to controls (P < 0.001). Serum BChE showed a significant increase and Zn was significantly decreased in different stages of breast cancer.
Conclusions: Both BChE and Zn are inexpensive and can easily be analyzed and may play a role in the management of breast cancer.
Keywords: Breast cancer, butyrylcholinesterase, zinc
|How to cite this article:|
Kumar R, Razab S, Prabhu K, Ray S, Prakash B. Serum butyrylcholinesterase and zinc in breast cancer. J Can Res Ther 2017;13:367-70
| > Introduction|| |
Breast cancer is most common cancer among women worldwide and is the main cause of cancer-related mortality. Its early diagnosis and treatment can significantly reduce the morbidity and mortality. A large number of serological, molecular markers such as cancer antigen 15-3, cancer antigen 27–29, and carcinoembryonic antigen have been proposed for breast cancer screening but most lack specificity, sensitivity, prognostic value, and cost effectiveness., So, there is a need to develop a simple and cost-effective biochemical marker for diagnosis/screening of breast cancer.
Cholinesterase is an enzyme which hydrolyses acetylcholine. Two types of cholinesterase with different biochemical properties have been identified in humans-true cholinesterase and pseudocholinesterase (butyrylcholinesterase [BChE]). True cholinesterase is found in the central nervous system, muscles and in erythrocytes. BChE is an alpha-glycoprotein found in the central and peripheral nervous system, in most tissues, and in the liver. BChE has a half-life of about 12 days., Increased activity of this enzyme has been reported in obesity, diabetes, uremia, hyperthyroidism, and in hyperlipidemic subjects., Studies have shown that BChE genes are aberrantly expressed in a variety of human cancers. Serum BChE has been linked to tumorigenesis, cell proliferation and cell differentiation.,,, BChE has been used as a biochemical marker in the management of head, neck, oral cell squamous carcinoma, and cervical cancers.
Zinc (Zn) acts as a cofactor for enzyme superoxide dismutase. As this enzyme is involved in the protection of cellular components against free radical-induced damage and carcinogenesis, Zn can act as cellular growth protector, including the growth of neoplastic cells. Zn stabilizes DNA and RNA polymerase, inhibits phosphodiesterase and activates adenylate cyclase suggesting its importance oncogenesis. Based on animal models, Zn deficiency has also been linked to initiation and malignant transformation in different cancers.,,, Further, Bhanumathy et al., demonstrated that enzyme BChE has two Zn binding sites and Zn is an effective inhibitor of enzyme BChE under normal physiological conditions indicating a possible synergy between these two in preventing or promoting cancer.,
Therefore, the aim of present study was to estimate and compare serum BChE and serum Zn levels in healthy controls and biopsy proven breast cancer patients before definitive therapy.
| > Subjects and Methods|| |
Permission from Institutional Ethics Committee and consent from participants were obtained before carrying out this study. This prospective cross-sectional study included 50 female patients who were newly diagnosed (preoperative) with breast cancer. All patients were nonsmokers, nonalcoholic, and were not on any long-term medications. None of the patients had any other serious medical or surgical illness. Controls consisted of 50 healthy females randomly selected from a group of healthy nonsmoking volunteers with no history of previous disease, drug, or alcohol consumption.
Blood samples were collected from all the subjects into empty red capped vacutainer and immediately stored on ice at 4°C. The serum was then separated and stored at −20°C until use. Serum was used for the measurement of BChE and Zn.
Estimation of serum butyrylcholinesterase
Acetylthiocholine was hydrolyzed by BChE to corresponding fatty acid and thiocholine. The rate of formation of thiocholine was monitored by continuous reaction of thiol group with 5,5'-dithio-bis-(nitrobenzoic acid) to form a yellow anion that was measured spectrophotometrically at 410 nm. Enzyme activity was calculated by molar absorption coefficient of the product of chemical reaction, 5-thio-2-nitrobenzoate (1.36 × mmol −1 × min −1 × cm −1).
Estimation of zinc
Zn in an alkaline medium reacts with nitro-phospho- adenosine phosphosulfate (PAPS) to form a purple colored complex. The intensity of the complex formed is directly proportional to the amount of Zn present in the sample.,,
Zn + nitro-PAPS purple colored complex
The data analysis was done by using SPSS statistic analyzer software Version 15.0 (Lenience-SPSS Bangalore, Southeast Asia) data was expressed as median and inter quartile range. Comparisons between different stages of cancer were done using Kruskal–Wallis test. Pairwise comparisons were done using Mann–Whitney U-test with Bonferroni correction for type I error.
| > Results|| |
There was a significant increase in serum levels of BChE and Zn in breast cancer patients compared to controls (P < 0.001) [Table 1].
|Table 1: Comparison of serum BChE and Zn levels in controls and breast cancer patients|
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Serum levels of BChE showed a significant increase between different stages of breast cancer except between stages 2 and 3 [Table 2]. Serum Zn was also significantly higher in stages 3 and 4 when compared with that of stage 2 (P < 0.001) [Table 3].
| > Discussion|| |
In the present study serum levels of BChE and Zn were compared between breast cancer patients and healthy controls. Our study showed the median value of serum BChE was significantly increased in breast cancer patients as compared to that of controls (P< 0.001) [Table 1]. There was also a significant increase in BChE values with the advancement of cancer [Table 2] supporting its role tumorigenesis as mentioned in previous studies. Similar studies have shown abnormal expression of both BChE and acetylcholinesterase, andin vivo amplification of their genes in intracranial neoplasms such as meningioma, glioma and acoustic neuromas, lung cancers, megakaryocytopoietic disorders, leukemia, and ovarian tumors. BChE can affect cell proliferation by virtue of its antiapoptotic effects and by its ability to enhance anchorage independent cell growth which helps in cancer metastasis.
It was also observed that median level of serum Zn was significantly lower in breast cancer patient than that of controls, and its levels were significantly decreased in stage 2 to stage 4 of cancer. These observation were accordance with Kuo et al., and other studies.,, They had concluded that Zn is required for the structural stability of Zn finger proteins (Zfps). These Zfp plays an important role in transcriptional regulation of cellular metabolic network, interacting with Zn binding domains such as Zn fingers, RING fingers, and LIM domains, which is critical for DNA synthesis, RNA transcription, cell division, and cell activation. The regulation of cell proliferation by Zn can occur at different levels including the requirement of Zn for the activity of enzymes involved in DNA synthesis (i.e. deoxythymidine kinase) and the modulation of regulatory signals directly, as well as indirectly, through its effects on the hormonal regulation of cell division. So, deficiency/decrease in Zn levels might have contributed to the dysregulation of these above pathways leading to carcinogenesis.
The findings of our study cannot be generalized as the sample size is very small. Also, serum BChE and Zn are not specific markers for breast cancer and their activity may alter in cancer of other tissues.
| > Conclusions|| |
As we have observed a significant increase in BChE and a significant decrease in Zn in breast cancer patients, they may have a role in the management of breast cancer. Further studies in a larger cohort can provide a definitive data about the prognostic role of these markers.
Financial support and sponsorship
This study was supported by Kasturba Medical College, Manipal Registration Number-ACCT/PGGRANT/2014-15.
Conflicts of interest
There are no conflicts of interest.
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[Table 1], [Table 2], [Table 3]