OBJECTIVES: Primary tumor treatment through surgical resection and adjuvant therapy has been extensively studied, but there is a lack of effective strategies and drugs for the treatment of tumor metastases. Here, we describe a functional product based on a combination of compounds, which can be used as an adjuvant therapy and has well-known mechanisms for inhibiting cancer metastases, improving anti-cancer treatment, and enhancing immunity and antioxidant capacity. Our designed combination, named MVBL, consists of four inexpensive compounds: L-selenium-methylselenocysteine (MSC), D-‍α‍-tocopheryl succinic acid (VES), β‍-carotene (β‍-Ca), and L-lysine (Lys). METHODS: The effects of MVBL on cell viability, cell cycle, cell apoptosis, cell migration, cell invasion, reactive oxygen species (ROS), and paclitaxel (PTX)-combined treatment were studied in vitro. The inhibition of tumor metastasis, antioxidation, and immune enhancement capacity of MVBL were determined in vivo. RESULTS: MVBL exhibited higher toxicity to tumor cells than to normal cells. It did not significantly affect the cell cycle of cancer cells, but increased their apoptosis. Wound healing, adhesion, and transwell assays showed that MVBL significantly inhibited tumor cell migration, adhesion, and invasion. MVBL sensitized MDA-MB-231 breast cancer cells to PTX, indicating that it can be used as an adjuvant to enhance the therapeutic effect of chemotherapy drugs. In mice, experimental data showed that MVBL inhibited tumor metastasis, prolonged their survival time, and enhanced their antioxidant capacity and immune function. CONCLUSIONS This study revealed the roles of MVBL in improving immunity and antioxidation, preventing tumor growth, and inhibiting metastasis in vitro and in vivo. MVBL may be used as an adjuvant drug in cancer therapy for improving the survival and quality of life of cancer patients.
Mice ; Animals ; beta Carotene ; Lysine/pharmacology* ; Antioxidants/pharmacology* ; Quality of Life ; Paclitaxel/pharmacology* ; Apoptosis ; alpha-Tocopherol ; Succinates/pharmacology* ; Cell Line, Tumor ; Cell Proliferation ; Neoplasms

This study was conducted in order to investigate the association between hypertension and oxidative stress-related parameters and to evaluate these parameters in subclinical hypertensive patients and normotensive subjects living in Korea. We attempted to determine whether oxidative stress-related parameters would differ between two groups of 227 newly-diagnosed, untreated (systolic blood pressure (BP) > or = 130 mmHg and diastolic BP > or = 85 mmHg) and 130 normotensive subjects (systolic BP < 120 mmHg and diastolic BP < 80 mmHg). General characteristics of the subjects were collected using a simple questionnaire. From subjects' blood, degree of DNA damage in lymphocytes, the activities of erythrocyte superoxide dismutase, catalase, and glutathione peroxidase, level of plasma total radical-trapping antioxidant potential (TRAP), glutathione, and anti-oxidative vitamins, as well as plasma lipid profiles and conjugated diene (CD) were analyzed. Evaluation of the associations of oxidative stress-related parameters with blood pressure of the subjects was performed using Pearson partial correlation and multivariate logistic regression analysis after adjusting for confounding factors. Several oxidative stress-related parameters were higher in subclinical hypertensive patients than in normotensive subjects. Plasma levels of alpha-tocopherol, beta-carotene, TRAP, and activity of GSH-px were significantly lower in subclinical hypertensive patients than in normotensive subjects. Increased levels of DNA damage, lipid peroxidation, triglyceride, total cholesterol, and LDL-cholesterol were observed in subclinical hypertensive patients. These results confirm an association between blood pressure and oxidative stress-related parameters and suggest that the pathogenic role of oxidative stress in hypertension might be significant.
alpha-Tocopherol ; beta Carotene ; Blood Pressure ; Catalase ; Cholesterol ; DNA Damage ; Erythrocytes ; Glutathione ; Glutathione Peroxidase ; Humans ; Hypertension ; Korea ; Lipid Peroxidation ; Logistic Models ; Lymphocytes ; Oxidative Stress ; Plasma ; Surveys and Questionnaires ; Superoxide Dismutase ; Vitamins

Pumpkins have considerable variation in nutrient contents depending on the cultivation environment, species, or part. In this study, the general chemical compositions and some bioactive components, such as tocopherols, carotenoids, and beta-sitosterol, were analyzed in three major species of pumpkin (Cucurbitaceae pepo, C. moschata, and C. maxima) grown in Korea and also in three parts (peel, flesh, and seed) of each pumpkin species. C. maxima had significantly more carbohydrate, protein, fat, and fiber than C. pepo or C. moschata (P < 0.05). The moisture content as well as the amino acid and arginine contents in all parts of the pumpkin was highest in C. pepo. The major fatty acids in the seeds were palmitic, stearic, oleic, and linoleic acids. C. pepo and C. moschata seeds had significantly more gamma-tocopherol than C. maxima, whose seeds had the highest beta-carotene content. C. pepo seeds had significantly more beta-sitosterol than the others. Nutrient compositions differed considerably among the pumpkin species and parts. These results will be useful in updating the nutrient compositions of pumpkin in the Korean food composition database. Additional analyses of various pumpkins grown in different years and in different areas of Korea are needed.
Arginine ; beta Carotene ; Carotenoids ; Cucurbita ; Fatty Acids ; gamma-Tocopherol ; Korea ; Linoleic Acid ; Linoleic Acids ; Nutritive Value ; Seeds ; Sitosterols ; Tocopherols

Glutathione S-transferase (GST) is a multigene family of phase II detoxifying enzymes that metabolize a wide range of exogenous and endogenous electrophilic compounds. GSTM1 and GSTT1 gene polymorphisms may account for inter-individual variability in coping with oxidative stress. We investigated the relationships between the level of lymphocyte DNA and antioxidative parameters and the effect on GST genotypes. GSTM1 and GSTT1 were characterized in 301 young healthy Korean adults and compared with oxidative stress parameters such as the level of lymphocyte DNA, plasma antioxidant vitamins, and erythrocyte antioxidant enzymes in smokers and non smokers. GST genotype, degree of DNA damage in lymphocytes, erythrocyte activities of superoxide dismutase, catalase, and glutathione peroxidase (GSH-Px), and plasma concentrations of total radical-trapping antioxidant potential (TRAP), vitamin C, alpha- and gamma-tocopherol, alpha- and beta-carotene, and cryptoxanthin were analyzed. Lymphocyte DNA damage assessed by the comet assay was higher in smokers than that in non-smokers, but the levels of plasma vitamin C, beta-carotene, TRAP, erythrocyte catalase, and GSH-Px were lower than those of non-smokers (p < 0.05). Lymphocyte DNA damage was higher in subjects with the GSTM1-null or GSTT1-present genotype than those with the GSTM1-present or GSTT1-null genotype. No difference in erythrocyte antioxidant enzyme activities, plasma TRAP, or vitamin levels was observed in subjects with the GSTM1 or GSTT1 genotypes, except beta-carotene. Significant negative correlations were observed between lymphocyte DNA damage and plasma levels of TRAP and erythrocyte activities of catalase and GSH-Px after adjusting for smoking pack-years. Negative correlations were observed between plasma vitamin C and lymphocyte DNA damage only in individuals with the GSTM1-present or GSTT1-null genotype. The interesting finding was the significant positive correlations between lymphocyte DNA damage and plasma levels of alpha-carotene, beta-carotene, and cryptoxanthin. In conclusion, the GSTM1-null and GSTT1-present genotypes as well as smoking aggravated antioxidant status through lymphocyte DNA damage. This finding confirms that GST polymorphisms could be important determinants of antioxidant status in young smoking and non-smoking adults. Consequently, the protective effect of supplemental antioxidants on DNA damage in individuals carrying the GSTM1-null or GSTT1-present genotypes might show significantly higher values than expected.
Adult ; Antioxidants ; Ascorbic Acid ; beta Carotene ; Carotenoids ; Catalase ; Comet Assay ; DNA ; DNA Damage ; Erythrocytes ; gamma-Tocopherol ; Genotype ; Glutathione ; Glutathione Peroxidase ; Glutathione Transferase ; Humans ; Lifting ; Lymphocytes ; Multigene Family ; Oxidative Stress ; Plasma ; Smoke ; Smoking ; Superoxide Dismutase ; Vitamins ; Xanthophylls ; Young Adult

Oxidative stress leads to the induction of cellular oxidative damage, which may cause adverse modifications of DNA, proteins, and lipids. The production of reactive species during oxidative stress contributes to the pathogenesis of many diseases. Antioxidant defenses can neutralize reactive oxygen species and protect against oxidative damage. The aim of this study was to assess the antioxidant status and the degree of DNA damage in Korean young adults using glutathione s-transferase (GST) polymorphisms. The GSTM1 and GSTT1 genotypes were characterized in 245 healthy young adults by smoking status, and their oxidative DNA damage in lymphocytes and antioxidant status were assessed by GST genotype. General characteristics were investigated by simple questionnaire. From the blood of the subjects, GST genotypes; degree of DNA damage in lymphocytes; the erythrocyte activities of superoxide dismutase, catalase, and glutathione peroxidase; plasma concentrations of total peroxyl radical-trapping potential (TRAP), vitamin C, alpha- and gamma-tocopherol, alpha- and beta-carotene and cryptoxanthin, as well as plasma lipid profiles, conjugated diene (CD), GOT, and GPT were analyzed. Of the 245 subjects studied, 23.2% were GSTM1 wild genotypes and 33.4% were GSTT1 wild genotype. No difference in erythrocyte activities of superoxide dismutase, catalase, or glutathione peroxidase, and the plasma TRAP level, CD, GOT, and GPT levels were observed between smokers and non-smokers categorized by GSTM1 or GSTT1 genotype. Plasma levels of alpha- and gamma-tocopherol increased significantly in smokers with the GSTT1 wild genotype (p < 0.05); however, plasma level of alpha-carotene decreased significantly in non-smokers with the GSTM1 wild genotype (p < 0.05). DNA damage assessed by the Comet assay was significantly higher in non-smokers with the GSTM1 null genotype; whereas DNA damage was significantly lower in non-smokers with the GSTT1 null genotype. Total cholesterol and LDL cholesterol levels were significantly higher in non-smokers with the GSTT1 null genotype than those with the GSTT1 wild genotype (p < 0.05). In conclusion, the GSTM1 null genotype or the GSTT1 wild genotype in non-smokers aggravated their antioxidant status through DNA damage of lymphocytes; however, the GSTT1 wild type in non-smokers had normal plasma total cholesterol and LDL-cholesterol levels. This finding confirms that GST polymorphisms could be an important determinant of antioxidant status and plasma lipid profiles in non-smoking young adults. Further study is necessary to clarify the antioxidant status and/or lipid profiles of smokers with the GST polymorphism and to conduct a study with significantly more subjects.
Ascorbic Acid ; beta Carotene ; Carotenoids ; Catalase ; Cholesterol ; Cholesterol, LDL ; Comet Assay ; DNA ; DNA Damage ; Erythrocytes ; gamma-Tocopherol ; Genotype ; Glutathione ; Glutathione Peroxidase ; Glutathione Transferase ; Humans ; Lymphocytes ; Oxidative Stress ; Plasma ; Proteins ; Surveys and Questionnaires ; Reactive Oxygen Species ; Smoke ; Smoking ; Superoxide Dismutase ; Xanthophylls ; Young Adult

To determine vitamin A and E intakes and their food sources, dietary intakes were collected by three consecutive 24-hour recalls from 192 adults living in Seoul and Gyeonggi Province, Korea. The mean vitamin A, retinol and beta-carotene intakes were 1240.1 +/- 1101.1 microg retinol equivalent/day (693.3 +/- 563.2 microg retinol activity equivalent/day), 182.6 +/- 149.5 microg/day and 5443.3 +/- 6365.5 microg/day, respectively. Only 9.4% of the subjects consumed less than the Korean Estimated Average Requirement for vitamin A. The mean vitamin E intake was 6.03 +/- 2.54 mg alpha-tocopherol equivalent/day. The alpha-tocopherol and gamma-tocopherol intakes were 4.83 +/- 2.03 and 5.57 +/- 3.41 mg/day, respectively. Most of the subjects (93.8%) consumed less than the Korean Adequate Intake for vitamin E. The major food sources of vitamin A were sweet potato, carrot, red pepper powder, spinach, and citrus fruit, and the top 30 foods provided 91.5% of total Plant foods provided 81.0% and animalderived foods 10.5% of the vitamin A intake from the top 30 foods. The major food sources of vitamin E were soybean oil, red pepper powder, Ramyeon (cup noodles), spinach, and egg. The top 30 foods provided 78.0% of total vitamin E intake. Plant foods provided 61.3% and animal-derived foods 15.9% of the vitamin E intake from the top 30 foods. In conclusion, the vitamin A intake of the Korean adults in this study was ge-nerally adequate, but the vitamin E intake of many subjects was inadequate. Therefore, nutritional education may be of benefit to Korean adults to increase their vitamin E intake.
Adult ; alpha-Tocopherol ; beta Carotene ; Capsicum ; Carotenoids ; Citrus ; Daucus carota ; gamma-Tocopherol ; Humans ; Ipomoea batatas ; Korea ; Ovum ; Plants ; Soybean Oil ; Spinacia oleracea ; Tocopherols ; Vitamin A ; Vitamin E ; Vitamins

Elevated plasma concentration of total homocysteine (ptHcy) is known as an independent risk factor of cardiovascular disease (CVD) and oxidative stress is also commonly implicated in CVD. An association between ptHcy and oxidative stress has recently been suggested. The study objective is to examine the relationship between ptHcy and oxidative stress markers in 103 healthy college students (62 males and 41 females). Plasma levels of ptHcy, oxidative stress markers (conjugated diene, erythrocyte catalase, TRAP, lymphocyte DNA damage), antioxidant vitamins (alpha-tocopherol, gamma-tocopherol, carotenoids), and lipid parameters (total cholesterol, triglyceride, HDL cholesterol) were determined. The results show that the concentration of ptHcy was significantly higher in male subjects (22.17 +/- 2.14 micromole/L) than in female subjects (12.28 +/- 0.45 micromole/L). There was a negative association between ptHcy and plasma beta-carotene in male subjects (p < 0.05), but no correlation between ptHcy and other plasma antioxidant vitamin levels in either gender. However, there were the negative correlations between ptHcy and plasma alpha-carotene or beta-carotene, and a positive correlation between ptHcy and lymphocyte DNA damage. A significantly low level of alpha-carotene or beta-carotene was found in male subjects with elevated ptHcy (> or = 15 micromol/L), as compared to those with lower plasma homocysteine. These study results confirmed the views on the association between plasma homocysteine and oxidative stress markers in humans and support the hypothesis that homocysteine promotes the oxidative environment by counteracting the antioxidant defense mechanism.
beta Carotene ; Cardiovascular Diseases ; Carotenoids ; Catalase ; Cholesterol ; DNA ; DNA Damage ; Erythrocytes ; Female ; gamma-Tocopherol ; Homocysteine ; Humans ; Lymphocytes ; Male ; Oxidative Stress ; Plasma ; Risk Factors ; Vitamins

PURPOSE:To investigate the change in the antioxidant vitamin levels in maternal uterine venous plasma (MUVP), amniotic fluid (AF), and chorioamnion after vitamin C and E supplementation during pregnancy. METHODS:Thirty pregnant women who were scheduled for elective cesarean section between 37 and 39 gestational weeks were randomized in this study. Fifteen women were given a daily oral dose of vitamin C 1,000 mg and vitamin E 400 IU from 33~34 gestational weeks to delivery. The other fifteen women were not given, as a control group. Maternal uterine venous blood, AF, and chorioamnion were obtained after cesarean section. Lipid peroxides and oxygen-radical absorbance capacity value were measured by thiobarbituric acid reaction and Cao's method respectively. Ascorbic acid, uric acid, beta-carotene, retinol, alpha-tocopherol, and gamma-tocopherol were measured by high performance liquid chromatography. The tissue sections of chorioamnion were stained with hematoxylin-eosin and Masson-trichrome stain, and immunohistochemical stain for collagen type IV was also performed. RESULTS:The lipid peroxide levels in MUVP of the study group were significantly lower than those of the control group but in contrast, ORAC (Oxygen-radical absorbance capacity) values were lower in the control group. The alpha-tocopherol levels in MUVP, AF, and chorioamnion study group were significantly higher than those of the control group. Amniotic membrane and subepithelial stromal tissue in the study group were thicker than those in the control group. And subchorionic type IV collagen of placenta tissue in the study group was more stained than that of the control group. CONCLUSION:Maternal vitamin C and E supplementation may be beneficial in the prevention of diseases caused by oxidative stress such as preeclampsia and PROM and in increasing fibrin and type IV collagen in chorioamnion.
alpha-Tocopherol ; Amnion ; Amniotic Fluid ; Ascorbic Acid ; beta Carotene ; Cesarean Section ; Chromatography, Liquid ; Collagen Type IV ; Female ; Fibrin ; gamma-Tocopherol ; Humans ; Lipid Peroxides ; Oxidative Stress ; Placenta ; Plasma ; Pre-Eclampsia ; Pregnancy ; Pregnant Women ; Thiobarbiturates ; Uric Acid ; Vitamin A ; Vitamin E ; Vitamins

OBJECTIVE: This controlled trial investigated the effect of supplementation with vitamins C and E on the lipid peroxide, antioxidant ability, and antioxidant vitamin levels in full term maternal and umbilical venous plasma. METHODS: Forty pregnant women were randomized in this study. They were nulliparous or multiparous women with history of preeclampsia or preterm premature rupture of membranes (PPROM). Twenty women were given vitamin C (1,000 mg/day) and vitamin E (400 IU/day) from 15~20 gestational weeks to delivery. The others were not given, as a control group. Maternal venous blood was obtained before vitamin supplementation and just before delivery. Umbilical venous blood was obtained after delivery. Lipid peroxide level and oxygen-radical absorbance capacity (ORAC) were measured by thiobarbituric acid reaction and Cao's method, respectively. Ascorbic acid, uric acid, beta-carotene, retinol, alpha-tocopherol, and gamma-tocopherol were measured by high performance liquid chromatography. Results: Supplementation with vitamins C and E was associated with decrease in lipid peroxide levels and increase in ORAC values and alpha-tocopherol levels in maternal venous plasma. And it was also associated with decrease in lipid peroxide levels and increase in ORAC values and alpha-tocopherol levels in umbilical venous plasma. CONCLUSION: Supplementation with vitamins C and E may be beneficial in the prevention of oxidant-antioxidant imbalance origin diseases such as preeclampsia, PPROM. And it also may affect antioxidant ability of the fetus.
alpha-Tocopherol ; Ascorbic Acid ; beta Carotene ; Female ; Fetus ; gamma-Tocopherol ; Humans ; Membranes ; Plasma ; Pre-Eclampsia ; Pregnant Women ; Rupture ; Thiobarbiturates ; Uric Acid ; Vitamin A ; Vitamin E ; Vitamins

The serum levels of antioxidant materials (alpha-carotene, beta-carotene, beta-cryptoxanthin, lutein, lycopene, alpha-tocopherol, gamma-tocopherol, retinol) of the healthy Korean middle-aged adults (n = 373) were measured and their relationships with the serum lipids and anthropometric indices were analyzed. The serum levels of beta-cryptoxanthin, beta-carotene, lutein were higher than those of lycopene and alpha-carotene. The levels of all measured carotenoids except lutein were significantly higher in females than in males, but retinol level was vice versa. There was a tendency of increase in serum levels of antioxidant vitamins with increasing age. The serum carotenoid levels had a positive correlation with serum cholesterol and a negative correlation with serum triglyceride. The serum levels of tocopherols or retinol showed a significantly positive relationship with blood cholesterol or triglyceride. In overall, anthropometric indices showed negative relations with serum carotenoids levels, but vice versa with serum tocopherol or retinol levels. Particularly, beta-carotene and lutein levels showed a significantly negative relation with blood pressure in male subjects. The serum levels of alpha-carotene, beta-carotene and beta-cryptoxanthin had significantly negative relations with body fat-related indices in female subjects. The results demonstrated that blood antioxidants levels differed by sex and age, and had significant relations with blood lipid levels and anthropometric indices. Therefore, the rationale and significance of the relationships need to be elucidated in the future study related to dietary intakes and life style.
Adult ; alpha-Tocopherol ; Antioxidants ; beta Carotene ; Blood Pressure ; Carotenoids ; Cholesterol ; Female ; gamma-Tocopherol ; Humans ; Korea ; Life Style ; Lutein ; Male ; Tocopherols ; Vitamin A ; Vitamins ; Xanthophylls