The purpose of this study was to investigate the effect of fermented mushroom of
Uterine cervical cancer is still the second most common cancer in women worldwide, despite the existence of effective screening methods [
In humans, selenium (Se) is a trace element nutrient which functions as cofactor for reduction of antioxidant enzymes such as glutathione peroxidases. Several studies have suggested a possible link between cancer and selenium deficiency [
This study was performed in accordance with the Guide for the Care and Use of Laboratory Animals. Care was taken to minimize discomfort, distress, and pain to the animals.
Female Kunming strain mice were maintained at room temperature under alternating natural light/dark photoperiod and had access to standard laboratory food and fresh water
Sodium selenite was dissolved in saline solution (0.9% NaCl). An ampule was filled with 0.4 mL of SS and then was sterilized in a microwave oven for 3 minutes.
Se-CS was prepared according to study of Zhang et al. [
The mycelia were harvested at the end of fermentation; then they were centrifuged at 12,000 g for 10 min and dried to constant weight at 60°C for sufficient time in laboratory vacuum ovens, and the dry weight of the mycelia was then measured.
Se-CS was dialyzed against distilled water for 96 h by changing the water every 12 h until no Se was detected in the dialyzing water. Thus, Se compounds left in the dialyzed sample were considered to be organic selenium. The Se content was determined using graphite furnace atomic absorption spectrophotometry introduced by Zhang et al. [
Se concentrations in liver and kidney were determined using atomic absorption spectrometer (AAS-3200, Shanghai, China). The standard of selenium was purchased from Anhui Star New Material Technology Co., Ltd, China. Weighed aliquots of frozen tissue were digested in 3 stages: the first using 5 mL mixed acids (4 : 1 nitric acid : perchloric acid), the second using a combination of 2 mL HNO3 and 30% H2O2, and finally using 2 mL HNO3. All digestion stages were performed at 130°C until the acid was completely evaporated and the residue dried before the next acid stage was started. After the third acid treatment, 1% HNO3 was added to the digests and heated at 80°C for 1 h. After cooling, the sample volume was measured and analyzed.
Murphy’s string method [
The impact of Se-CS on immune organ was evaluated based on the thymus index and spleen index [
In uterus tissues, lactate dehydrogenase (LDH) was estimated using a method described by Lum and Gambino [
All data were analyzed by a one-way analysis of variance, and the differences between means were established by Duncan’s multiple-range test. The data represents means and standard deviations. The significant level of 5% (
Se can be accumulated by CS even from low external concentrations (Figure
The effect of Se on growth of
The determination of selenium in mycelia obtained in the absence and in the presence of Se in medium demonstrated the incorporation of element to fungal cells (Figure
The content of Se in the mycelia. The content of Se accumulated in the mycelia was 4789.26 ± 13.0
The mice did not suffer from any apparent toxic effect of Se-0.4 during the observation period. Only a small number of mice died in certain groups (Table
Effect of SE-CS and other treatments on survival of MCA-treated mice.
Different groups | Number of mice |
|
---|---|---|
Initial | Final | |
MCA-treated | 12 | 7 |
MCA and Se-0.4-treated | 12 | 10 |
MCA and Se-0-treated | 12 | 10 |
MCA and SS-treated | 12 | 9 |
Control group | 12 | 11 |
MCA-induced group administered orally saline showed 85.7% tumor incidence, whereas MCA and Se-0.4 group showed 40% tumor incidence (
Effect of SE-CS and other treatments on tumor incidence induction by MCA.
Different groups | Number of |
Number of mice with |
Tumor |
---|---|---|---|
MCA-treated | 7 | 6 | 85.7 |
MCA and Se-0.4-treated | 10 | 4 | 40* |
MCA and Se-0-treated | 10 | 7 | 70 |
MCA and SS-treated | 9 | 7 | 77.7 |
Control group | 11 | 0 | 0 |
As shown in Table
The effect of SE-CS on immune function (
Different groups | Number of mice |
Thymus |
Spleen |
---|---|---|---|
MCA-treated | 7 |
|
|
MCA and Se-0.4-treated | 10 |
|
|
MCA and Se-0-treated | 10 |
|
|
MCA and SS-treated | 9 |
|
|
Control group | 11 |
|
|
The organ masses of liver and kidney were significantly different between SS and Se-CS group (
Effects of Se-CS on organ masses of mice (
Mouse group | Number of mice |
Liver |
Kidney |
---|---|---|---|
Control group | 7 |
|
|
MCA-induced group | 10 |
|
|
MCA and SS group | 10 |
|
|
MCA and Se-0 group | 9 |
|
|
MCA and Se-0.4 group | 11 |
|
|
The different letters in the same column indicate a statistical difference (
The Se contents in animal tissues were measured following the studies and the results are shown in Figure
Se (ppm) in animal tissues (
LDH was measured to evaluate the role of antioxidative stress in the protection of Se-CS. A significant increase in the activity of LDH in serum was observed in MCA group, as compared to the control group (
Effect of SE-CS and other treatments on serum LDH, GSH, and LPO levels.
Different groups ( |
LDH (IU/L) | GSH (nmol/mg protein) | nmol/g protein |
---|---|---|---|
Control (7) |
|
|
|
MCA-induced group (10) |
|
|
|
MCA and SS group (10) |
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|
MCA and Se-0 group (9) |
|
|
|
MCA and Se-0.4 group (11) |
|
|
|
Values are shown as means ± SEM.
Activities of various antioxidant enzymes and Na+/K+-ATPase of different groups have been listed in Table
Effect of SE-CS and other treatments on the activity of various enzymes (nmol/g protein).
Different groups ( |
GPx | GR | GST | CAT | Na+K+-ATPase |
---|---|---|---|---|---|
Control (7) |
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MCA-induced group (10) |
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MCA and SS group (10) |
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|
MCA and Se-0 group (9) |
|
|
|
|
|
MCA and Se-0.4 group (11) |
|
|
|
|
|
Values are shown as means ± SEM.
In the current study, we investigated the potential therapeutic efficacy of Se-CS for cervical cancer. Se is required in biosynthesis of important selenoenzymes. Some of them are active as catalysts for reduction of extracellular oxidants, thereby protecting cells from potential damage by these hazardous compounds. CS is recognized as a dietary supplement recommended in many countries as a cancer therapeutic. So the coeffect of CS and selenium on uterine cervix cancer was studied.
During the production of Se-CS, the biomass of mycelia was significantly influenced by the Se in the medium (Figure
Survival of animals receiving Se-CS was significantly longer than the groups receiving only CS or Se. The shortest survival times were observed in the no treatment group. The findings of the present study demonstrate that oral administration of Se-CS during the process of MCA-induced uterine cervix cancer results in significant reduction in the occurrence of cervical carcinomas (
However, Se is also known to be toxic with a narrow range separating chronic conditions of deficiency and toxicity. The molecular toxicity of inorganic selenium was described in relation to its interaction with endogenous –SH groups. The animal studies have demonstrated that liver and kidney are the major target organs of Se toxicity [
Previous reports have shown that immunosuppression can be clearly detected in both cancer patients and tumor-bearing animals, demonstrating that the immune system plays an important role in immunosurveillance against malignant cells [
It has been proposed that antioxidant changes reflect an altered redox balance in several pathological states [
Collectively, our results indicate that Se-CS may represent a novel protective strategy against uterine cervical cancer by attenuating oxidative stress and improving immune function in MCA mice. However, the antitumor effect of Se-CS-0 and SS was not significant. It is implied that the antitumor effect was caused by the coeffect of CS and Se. Furthermore, our results also emphasize that Se-CS is less toxic to mice than SS. This finding suggested that the concomitant use of Se and CS could be a potential therapeutic approach to improve the efficacy of therapy for uterine cervical cancer.
The authors declare that there is no conflict of interests.
This work was supported by the National Science Youth Foundation of China (no. 81001162).