Serum selenium concentration and antioxidant activity in cervical cancer patients before and after treatment
Aim - in the present study, the effect of chemo and radio therapies on serum trace elements content and antioxidant activity in blood serum of cervical cancer patients was evaluated. Among 104 cervical cancer patients selected for the present study, 54 and 50 patients were treated with chemo- and ra...
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irk-123456789-1452122019-01-20T01:23:40Z Serum selenium concentration and antioxidant activity in cervical cancer patients before and after treatment Subramanyam D. Subbaiah, K.C.V. Rajendra W. Lokanatha V. Original contributions Aim - in the present study, the effect of chemo and radio therapies on serum trace elements content and antioxidant activity in blood serum of cervical cancer patients was evaluated. Among 104 cervical cancer patients selected for the present study, 54 and 50 patients were treated with chemo- and radiotherapy respectively. Plasma Se, Zn, Cu and some enzymatic antioxidants activities were estimated in serum before and after the treatment. The decreased levels of serum trace elements, glutathione peroxidase activity and total antioxidant capacity, and increased malondialdehyde, glutathion reductase was observed in cervical cancer patients when compared to healthy controls. The increased concentration of serum Se, Zn was observed in patients treated with chemotherapy. Simultaneously there was a significant (P << 0,001) increase in glutathione peroxidase and total antioxidant capacity, and significant decrease (P << 0,05) in malondialdehyde and glutathion reductase levels in the serum of patients treated with chemotherapy compared to the patients treated with radiotherapy. Key Words: cervical cancer, free radicals, glutathione peroxidase, selenium, chemotherapy, radiotherapy. 2013 Article Serum selenium concentration and antioxidant activity in cervical cancer patients before and after treatment / D. Subramanyam, K.C.V. Subbaiah, W. Rajendra, V. Lokanatha // Experimental Oncology. — 2013. — Т. 35, № 2. — С. 97-100. — Бібліогр.: 30 назв. — англ. 1812-9269 http://dspace.nbuv.gov.ua/handle/123456789/145212 en Experimental Oncology Інститут експериментальної патології, онкології і радіобіології ім. Р.Є. Кавецького НАН України |
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Original contributions Original contributions Subramanyam D. Subbaiah, K.C.V. Rajendra W. Lokanatha V. Serum selenium concentration and antioxidant activity in cervical cancer patients before and after treatment Experimental Oncology |
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Aim - in the present study, the effect of chemo and radio therapies on serum trace elements content and antioxidant activity in blood serum of cervical cancer patients was evaluated. Among 104 cervical cancer patients selected for the present study, 54 and 50 patients were treated with chemo- and radiotherapy respectively. Plasma Se, Zn, Cu and some enzymatic antioxidants activities were estimated in serum before and after the treatment. The decreased levels of serum trace elements, glutathione peroxidase activity and total antioxidant capacity, and increased malondialdehyde, glutathion reductase was observed in cervical cancer patients when compared to healthy controls. The increased concentration of serum Se, Zn was observed in patients treated with chemotherapy. Simultaneously there was a significant (P << 0,001) increase in glutathione peroxidase and total antioxidant capacity, and significant decrease (P << 0,05) in malondialdehyde and glutathion reductase levels in the serum of patients treated with chemotherapy compared to the patients treated with radiotherapy. Key Words: cervical cancer, free radicals, glutathione peroxidase, selenium, chemotherapy, radiotherapy. |
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Subramanyam D. Subbaiah, K.C.V. Rajendra W. Lokanatha V. |
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Subramanyam D. Subbaiah, K.C.V. Rajendra W. Lokanatha V. |
| author_sort |
Subramanyam D. |
| title |
Serum selenium concentration and antioxidant activity in cervical cancer patients before and after treatment |
| title_short |
Serum selenium concentration and antioxidant activity in cervical cancer patients before and after treatment |
| title_full |
Serum selenium concentration and antioxidant activity in cervical cancer patients before and after treatment |
| title_fullStr |
Serum selenium concentration and antioxidant activity in cervical cancer patients before and after treatment |
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Serum selenium concentration and antioxidant activity in cervical cancer patients before and after treatment |
| title_sort |
serum selenium concentration and antioxidant activity in cervical cancer patients before and after treatment |
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Інститут експериментальної патології, онкології і радіобіології ім. Р.Є. Кавецького НАН України |
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2013 |
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Original contributions |
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| citation_txt |
Serum selenium concentration and antioxidant activity in cervical cancer patients before and after treatment / D. Subramanyam, K.C.V. Subbaiah, W. Rajendra, V. Lokanatha // Experimental Oncology. — 2013. — Т. 35, № 2. — С. 97-100. — Бібліогр.: 30 назв. — англ. |
| series |
Experimental Oncology |
| work_keys_str_mv |
AT subramanyamd serumseleniumconcentrationandantioxidantactivityincervicalcancerpatientsbeforeandaftertreatment AT subbaiahkcv serumseleniumconcentrationandantioxidantactivityincervicalcancerpatientsbeforeandaftertreatment AT rajendraw serumseleniumconcentrationandantioxidantactivityincervicalcancerpatientsbeforeandaftertreatment AT lokanathav serumseleniumconcentrationandantioxidantactivityincervicalcancerpatientsbeforeandaftertreatment |
| first_indexed |
2025-07-10T21:06:56Z |
| last_indexed |
2025-07-10T21:06:56Z |
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| fulltext |
Experimental Oncology ��� ������� ���� ���ne���� ������� ���� ���ne� ���ne� ��
SERUM SELENIUM CONCENTRATION AND ANTIOXIDANT ACTIVITY
IN CERVICAL CANCER PATIENTS BEFORE AND AFTER TREATMENT
D. Subramanyam1, K.C.V. Subbaiah1, W. Rajendra2, V. Lokanatha1*
1Department of Biotechnology, Dravidian University, Kuppam 517426, AP, India
2Department of Zoology, Sri Venkateswara University, Tirupati 517502, AP, India
Aim: In the present study, the effect of chemo and radio therapies on serum trace elements content and antioxidant activity in blood
serum of cervical cancer patients was evaluated. Methods: Among 104 cervical cancer patients selected for the present study, 54 and
50 patients were treated with chemo- and radiotherapy respectively. Plasma Se, Zn, Cu and some enzymatic antioxidants activities
were estimated in serum before and after the treatment. Results: The decreased levels of serum trace elements, glutathione peroxidase
activity and total antioxidant capacity, and increased malondialdehyde, glutathion reductase was observed in cervical cancer patients
when compared to healthy controls. The increased concentration of serum Se, Zn was observed in patients treated with chemothera-
py. Simultaneously there was a significant (P < 0.001) increase in glutathione peroxidase and total antioxidant capacity, and signifi-
cant decrease (P < 0.05) in malondialdehyde and glutathion reductase levels in the serum of patients treated with chemotherapy
compared to the patients treated with radiotherapy. Conclusion: The results demonstrated that chemotherapy but not radiotherapy
results in significant increase in the trace elements levels and antioxidant activities in blood serum of cervical cancer patients.
Key Words: cervical cancer, free radicals, glutathione peroxidase, selenium, chemotherapy, radiotherapy.
Cervical cancer is one of the most prevalent can-
cers world-wide and the most recent compilation
of data indicates that an estimated 4������� new
cervical cancer cases occ�r ann�ally among women
world-wide. H�man papilloma vir�s is the main ca�s-
ative agent for the cervical cancer along with some
other risk factors. It is acknowledged that reactive spe-
cies �ROS� play an important role in many pathological
conditions incl�ding cancer. Under normal conditions
their harmf�l effects �pon the cells are ne�tralized
to a large extent by a cascade of antioxidant defense
mechanisms of the body. When overwhelming genera-
tion of ROS malf�nction of antioxidant balance occ�rs
in the body� the system is considered to be in a state
of oxidative stress [�]. It has been stated that genera-
tion of ROS d�ring cancer development interferes with
organ f�nctions directly by damaging proteins� fats
and n�cleotides [�].
Antioxidant s�pplementation d�ring radiation
therapy possesses a con�ndr�m for the radiation on-
cologist� as antioxidants that defend normal cells from
reactive oxygen species may provide the same ben-
efits to cancer cells and red�ce the efficacy of treat-
ment. Short- and long-term inj�ry to normal healthy
cells� incl�ding tiss�e damage and risk of oncogenic
transformation [�]� can be prevented by antioxidants.
New findings that antioxidants ind�ce apoptosis in t�-
mor cells and protect patients from severe side effects
of radiation treatment may prove these compo�nds
�sef�l in f�t�re adj�vant therapy.
At optimal doses� the radiation �sed in therapy
depletes cell�lar alphatocopherol in normal cells�
thereby increasing their risk of damage; animal st�d-
ies show that whole-body expos�re to X-ray irradiation
decreases the concentrations of vitamins C and E in tis-
s�es [4]. A decline in tiss�e vitamin E and Se d�ring
radiation therapy for breast cancer and a fall in vitamins
A� C� E� and Se d�ring breast cancer treatment with
ROS-prod�cing adriamycine may increase normal
tiss�e sensitivity to radiation damage.
Seleni�m is one of the key components of anti-
oxidative mechanism which belongs to every cell� and
there is evidence that this essential trace element have
anticancer properties. The large body of evidence
s�ggested the protective role of seleni�m �Se� in dif-
ferent cancers incl�ding cervical cancer. Se exerts
its chemopreventive effect in different ways� s�ch
as a defense against oxidative damage by scaveng-
ing the ROS and improves the synthesis of enzymatic
antioxidant gl�tathione peroxidase �GPx� [�� 6]. The
cytosolic GPx is the best selenoprotein� characterized
in mammalian cells� capable of red�cing eq�ivalents
from gl�tathione to detoxify hydrogen and lipid per-
oxidation [�]. In relation to the fortification with Se�
it has been demonstrated that Se and vitamin E �toco-
pherol� are interrelated in the in vivo antioxidant system
by a do�ble way� first� the formation of GPx contrib�tes
to the decomposition of lipid hydroperoxides into
non-pro-oxidant species; second� tocopherol acts
as a chain-breaking antioxidant [8� �].
Therefore� the present st�dy eval�ated the effect
of chemo and radiotherapy on ser�m trace element
levels and antioxidant capacity in cervical cancer
patients.
MATERIALS AND METHODS
Sample collection. Ser�m samples of cervical
cancer patients were collected from the Govern-
ment Maternity Hospital� Tir�pati� and Department
of Radiation Oncology� Government General Hos-
pital� G�nt�r� Andhra Pradesh. The pop�lation in-
Received: March 5, 2013.
*Correspondence: Fax: +91085-702-782-30
E-mail: lokanathav@yahoo.co.in
Abbreviations used: Gpx — glutathione peroxidase; GR — glutathione
reductase; MDA — malondialdehyde; ROS — reactive oxygen species.
Exp Oncol ����
��� �� ������
�8 Experimental Oncology ��� ������� ���� ���ne�
cl�ded ��4 ��4+��� cervical cancer patients� aged
�� to �� years �46.��±4 years�� randomly collected
from the hospitals. Ser�m samples from age matched
�� healthy donors ������ years� were collected
as control samples. The incl�sion criteria for the se-
lection of cervical cancer patients were proven by the
biopsy/histopathology� these patients had any other
pathologies and were treated only with chemotherapy
or radiotherapy.
For histopathological analysis� t�mors were classi-
fied according to TNM classification system [��]. From
��4 cervical cancer patients� �4 patients were treated
with chemotherapy �cisplatin + mitomycin� and �� pa-
tients were treated with radiotherapy �Cent Gy/sec�.
Ethical approval. The experimental protocol and
ethical aspects were approved by the Instit�tional
Ethical Committee �IEC�� Sri Venkateswara Medical
College� Tir�pati along with the patient consent forms.
Biochemical studies. Approximately � ml of blood
was collected before and after treatment �chemo-
or radiotherapy�. Ser�m was separated from the blood
and stored at -4� °C �ntil analysis.
Atomic adsorption spectroscopy was �sed to ana-
lyze the concentration of ser�m trace elements like Se
[��]� zinc and copper [��]. The GPx activity [��] and
total antioxidant ability [�4] was meas�red by spectro-
photometric method. Ser�m malondialdehyde �MDA�
was determined by the method [��] and gl�tathione
red�ctase �GR� activity was meas�red in the ser�m
by the method described in [�6].
Statistical analysis. The data were analysed �s-
ing a statistical package for social sciences �SPSS
��.� version�. A one way ANOVA was performed
followed by T�key’s test for comparison of res�lts
between control and experimental gro�ps. All val�es
were expressed as mean±S.E.
RESULTS
In this st�dy� ��4 cervical cancer patients were
selected for therapy based on their t�mor stage and
clinicopathological indexes �Table ��. All these pa-
tients had decreased levels of trace elements� GPx
and total antioxidant activity compared to the healthy
controls �Table ��. Increased concentration of ser�m
trace elements was observed in patients treated with
chemotherapy �P < �.��� vers�s patients treated
with radiotherapy. Interestingly� there was significant
�P < �.���� increase in the activity of total antioxidant
activity ��.��±�.��� and GPx ��8.�±�.8�� in patients
treated with chemotherapy� and there is no significant
change in these indexes ��.��±�.�4 and 4�.�±�.���
in radiotherapy treated patients.
The lipid peroxidation prod�ct� i.e. MDA levels� and
GR were fo�nd to be increased ���.��±�.6� µl/l and
�8.��±4.6� U/l� significantly in the ser�m of the pa-
tients with cervical cancer compared to the controls
���.86±�.8� µl/l and 48.6�±�.�� U/l�� b�t there is no sig-
nificant changes in these indexes after the co�rses
of chemotherapy or radiotherapy. However� after che-
motherapy� the decreased MDA and GR levels were
registered compared to radiotherapy-treated gro�p.
Table 1. Characteristics of cervical cancer patients
№ Character Patients, n
1 Median age (range), years 104 (30–75)
2 Stage of cervical cancer
IIA 16
IIB 28
IIIA 34
IIIB 18
IV 8
3 Histological features
SCC 64
DSCC 12
M.D/WDSCC 6/15
Du SCC 4
In. SCC 3
4 Lymphnode involvement 26
No involvement of lymphnode 78
5 Treatment
Chemotherapy (cisplatin + mitomycin) 54
Radiotherapy
(80 centi Gy/30 sec — min. per cycle)
50
Notes: SCC — squamous cell carcinoma; DSCC — differentiated squamous
cell carcinoma; M.D/WD SCC — moderately and well differentiated squamous
cell carcinoma; Du SCC — ductal squamous cell carcinoma; In. SCC — inter-
mediate squamous cell carcinoma.
Table 2. Serum levels of trace elements and antioxidant status of cervical
cancer patients before and after treatment
No Parameter Healthy con-
trols (n = 50)
Before
treatment
(n = 104)
After treatment
Chemothera-
py (n = 54)
Radiothera-
py (n = 50)
1 Se (µg/dl) 13.83 ± 0.21 7.32 ± 0.59* 11.16 ± 0.32* 8.90 ± 1.23*
2 Zn (µg/dl) 89.45 ± 0.32 56.32 ± 0.43* 83.62 ± 4.76* 59.98 ± 2.76*
3 Cu (µg/dl) 98.76 ± 2.43 72.15 ± 2.8* 73.13±2.6*** 72.54±2.6***
4 Mn (µg/dl) 0.54 ± 0.12 0.23 ± 0.18* 0.49 ± 1.2* 0.32 ± 0.23*
5 GPx (nmol/
NADPH/min/
mg protein)
62.5 ± 3.82 42.4 ± 4.63* 58.2 ± 7.82* 43.2 ± 2.32**
6 MDA (µl/l) 8.89 ± 1.52 15.99 ± 2.63* 11.86±1.89 ** 14.78±0.54**
7 GR (U/l) 24.63 ± 0.46 58.59 ± 4.62 * 48.63±2.32** 54.41±1.56**
8 TAC (mmol/l) 3.34 ± 0.23 1.02 ± 0.46* 2.89 ± 0.12* 1.23 ± 0.34**
Notes: Values are mean ± SE. Values with different superscripts differ signi-
ficantly from values within the same row, by ANOVA and Tukey’s tests. *Sig-
nificant at P < 0.001; **significant at P < 0.05 and ***unsignificant; GPx —
glutathione peroxidase; TAC — total antioxidant capacity; MDA — malondial-
dehyde, GR — glutathione reductase.
Correlation between Se and GPx. Ser�m sele-
ni�m was correlated with GPx at different levels� corre-
lation val�es is �.�� in healthy samples vers�s �.�� and
�.6� in chemo- or radiotherapy treated patients
respectively �Fig. � and ��. This correlation indicated
that increased concentration of ser�m Se increases
the antioxidant enzyme GPx� which is a seleni�m de-
pendent antioxidant.
38
39
40
41
42
43
44
4 5 6 7 8 9
Selenium
G
Px
Fig. 1. Correlation c�rve between Se and GPx after the che-
motherapy
Experimental Oncology ��� ������� ���� ���ne���� ������� ���� ���ne� ���ne� ��
0
10
20
30
40
50
60
4 5 6 7 8 9
Selenium
G
Px
Fig. 2. Correlation c�rve between Se and GPx after the radio-
therapy
DISCUSSION
Chemotherapy involves administration of cyto-
toxic dr�gs that prevents growth and proliferation
of neoplastic cell. Se is an antioxidant agent: it can
can red�ce hydrogen peroxides� lipid and phospho-
lipids hydroperoxides via GPx� thereby dampening the
propagation of free radicals and ROS.
In the present st�dy� decreased ser�m trace ele-
ments� especially Se levels were observed in cervical
cancer patients as compared to healthy controls
�Table ��. This is in accordance with observations that
the patients with Crohns disease and cancer [��� �8]
have significantly lowered ser�m Se than the controls.
The epidemiological data s�ggest that cancer morta-
lity is inversely correlated with Se cons�mption and that
people living in geographic areas with low Se content
have higher rate of malignancies� especially gastroin-
testinal and breast cancer [��].
There is no significant effect of radiotherapy
on antioxidant and trace elements in cervical cancer
patients. A recent st�dy has demonstrated that there
is no considerable change in ser�m antioxidant levels
after radiotherapy in cervical cancer patients [��]. O�r
res�lts were similar: no significant change in ser�m
antioxidant levels especially GPx and total antioxidant
activity after radiotherapy were fo�nd. However� after
the chemotherapy� 8�% of the patients have shown in-
creased concentration of Se� Zn and Mn accompanied
by GPx and total antioxidant activities. The similar find-
ings were reported in the st�dy [��] which indicated
that GPx activity was significantly increased in breast
cancer patients after chemotherapy. Fig. � and � show
that there is correlation between ser�m Se and GPx
in chemo and radiotherapy treated patients. The in-
creased Se concentration may be attrib�ted to the
exogeno�s s�pplementation of dr�gs. Increased
Se in ser�m of cancer patients ind�ces the increased
prod�ction of Se dependent antioxidant mechanism
like GPx� hence in the present st�dy GPx and total anti-
oxidant activity was increased in chemotherapy treated
patients compared to radiotherapy treated patients.
It is well established that antioxidant defense
system scavenges the free radicals directly or inter-
feres with the generation of free radical mediated
events inhibiting the neoplastic process [��]. In the
present st�dy� the ser�m antioxidant enzyme� i.e.
MDA and GR activity was fo�nd to be increased
significantly in patients with cervical cancer. Similar
reports of raised antioxidant enzyme activities have
been reported in patients with prostate cancer [��].
Gl�tathione red�ctase� an oxidative stress ind�cible
enzyme� plays a considerable role in the peroxyl sca-
venging mechanism and in maintaining the f�nctional
integration of the cell membranes. The rise in the acti-
vity of GR co�ld be d�e to its ind�ction to co�nter the
effect of increased oxidative stress.
In the present st�dy� a significant elevation of se-
r�m MDA in cervical cancer patients in comparison
to healthy controls has been observed. The reason for
increased lipid peroxidation co�ld be d�e to increased
generation of reactive oxygen species or s�ppres-
sion of the antioxidants defence mechanism in the
metabolically active tiss�es. Recently it was reported
the antioxidant defence was s�ppressed in vario�s
colorectal cancer t�mors [�4].
Seleni�m is an essential trace element for animals
incl�ding h�mans� has been shown to affect the f�nc-
tion of selenoproteins by being a part of active site
in antioxidant enzymes like gl�tathione peroxidase
and thioredoxin red�ctase. F�rthermore Se can acts
as anticancer agent thro�gh the pla�sible mechanisms
like stim�lation of imm�ne system and inhibition of cell
proliferation [��]. The s�stainable pers�asive evidence
indicates that Se can certainly play an important role
in cancer prevention [�6].
M�ltiple lines of experimental evidence indicated
that optimal s�pplementation with Se red�ces p�lmo-
nary metastasis of melanoma in mice [��]. Res�lts
obtained with the gene therapy approach clearly
demonstrated that CH�SeH can inhibit t�mor growth
and prolong host s�rvival rate [�8]. The prevention
of t�mor cell adhesion and migration is related to inhi-
bition of t�mor cell invasion into basement membrane
[��]. It was also doc�mented that brief pre-expos�re
of HeLa cells to micromolar concentration of selenite
res�lted in a dose dependent decrease in the rate
of their s�bseq�ent attachment to a solid matrix [��].
F�rther� the present findings also reveal a remarkable
relationship between levels of trace elements vers�s
antioxidants enzymatic system� especially Se vers�s
GPx and the concentration of Se is directly proportional
to the GPx activity. Consistent with the above findings
it is important to maintain a constant balance in ser�m
trace elements like Se in cancer patients which ind�ces
the enhancement of antioxidant enzymes.
In concl�sion� we have registered the decreased
concentration of trace elements� Se� GPx activity and
increased activity of lipid peroxidation� GR in cervical
cancer patients. However these indexes were sig-
nificantly improved after chemotherapy b�t not radio-
therapy. Hence� chemotherapy promotes an increase
of the antioxidant defense.
CONFLICT OF INTEREST
The a�thors declare no conflict of interest.
��� Experimental Oncology ��� ������� ���� ���ne�
ACKNOWLEDGEMENTS
The a�thors are thankf�l to Dr. D.S. Raj� Naid� and
Dr. P. Chandra Sekharan for providing cervical can-
cer samples. The a�thors also thanks to Instit�tional
Ethical committee �IEC�� S.V. Medical College� for
providing ethical clearance and UGC-BSR-Non-SAP
for providing financial assistance.
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