ascorbic-acid and Uterine-Neoplasms

Approximately 90 epidemiologic studies have examined the role of vitamin C or vitamin-C-rich foods in cancer prevention, and the vast majority have found statistically significant protective effects. Evidence is strong for cancers of the esophagus, oral cavity, stomach, and pancreas. There is also substantial evidence of a protective effect in cancers of the cervix, rectum, and breast. Even in lung cancer, for which carotenoids show a consistent protective effect, there is recent evidence of a role for vitamin C. Vitamin C is an important antioxidant and free radical scavenger in plasma and acts to regenerate active vitamin E in lipid membranes. Although several different factors in fruits and vegetables probably act jointly, the epidemiologic and biochemical evidence indicate an important role for vitamin C.

Topics: Ascorbic Acid; Epidemiologic Methods; Female; Gastrointestinal Neoplasms; Humans; Lung Neoplasms; Neoplasms; Stomach Neoplasms; Urogenital Neoplasms; Uterine Neoplasms

Most interventions aimed at reducing bleeding during myomectomy lack sufficient evidence regarding their effectiveness. Recently, it was reported that intraoperative ascorbic acid administration effectively reduced blood loss during abdominal myomectomy. Therefore, this study aimed to investigate whether intravenous ascorbic acid infusion would affect intraoperative blood loss in women undergoing laparoscopic myomectomy.. A randomized, double-blind, parallel-group, placebo-controlled trial including 50 women undergoing laparoscopic myomectomy was conducted. Women with ≤4 myomas, ≤9cm in maximum diameter were eligible. The study:control group ratio was 1:1. Starting 30minutes before anesthesia, 2g of ascorbic acid or a placebo were administered for 2hours intraoperatively. Intraoperative blood loss, the primary endpoint, was calculated as the difference between the volume of fluids acquired from suction and that used for irrigation of the abdominal cavity during surgery using constant values.. Among the 50 randomized women, 1 and 3 in the study and control groups, respectively, were excluded due to withdrawal of consent, cancelation of surgery, or non-measurement of the primary endpoint. The baseline and operative characteristics were similar between the study and control groups, as was the intraoperative blood loss (193±204mL vs. 159±193mL, P=0.52). In addition, the operating time (95±29min vs. 110±52min; P=0.50) and decrease in hemoglobin level after surgery (1.9±1.31g/dL vs. 1.4±1.4g/dL; P=0.24) were similar between the study and control groups.. Intravenous ascorbic acid infusion did not reduce intraoperative blood loss in women undergoing laparoscopic myomectomy.. ClinicalTrials.gov, www.clinicaltrials.gov, NCT01715597.

Topics: Adult; Ascorbic Acid; Blood Loss, Surgical; Double-Blind Method; Female; Humans; Infusions, Intravenous; Leiomyoma; Middle Aged; Operative Time; Treatment Outcome; Uterine Myomectomy; Uterine Neoplasms

To assess the usefulness of using ascorbic acid (vitamin C) administration in abdominal myomectomy.. A total of 102 patients were divided two groups in this prospective, clinical trial. Group A had received 2 g of ascorbic acid during a myomectomy, and group B had a myomectomy without any interventions. The operative time, blood loss, days of hospitalization, post-operative complications and rate of blood transfusions were compared between the two groups.. The blood loss (521.44 ± 199.24 vs. 932.9 ± 264.38 ml; p value <0.001), duration of the operation time (42 ± 13.9 vs. 68 ± 21.7 min; p value <0.001), days of hospitalization (2.7 ± 0.69 vs. 3.1 ± 0.59 days; p value 0.002) in group A were significantly less than in group B (p value 0.001). The chance risk ratio of a blood transfusion in group A was 0.4 (7.7 vs. 18% 95% CI of 0.1-1; p value 0.07). There was a significant correlation between the volume of bleeding and post-operative complications in both groups (p value in group A = 0.03; in group B = 0.004).. The administration of ascorbic acid (vitamin C) in abdominal myomectomy could reduce the blood loss during the procedure, operation time and days of hospitalization.

Topics: Adult; Antioxidants; Ascorbic Acid; Blood Loss, Surgical; Blood Transfusion; Female; Gynecologic Surgical Procedures; Hospitalization; Humans; Infusions, Intravenous; Leiomyoma; Postoperative Complications; Uterine Neoplasms

The anticancer activity of 8-hydroxyquinolines relies on complex formation with redox active copper and iron ions. Here we employ UV-visible spectrophotometry and EPR spectroscopy to compare proton dissociation and complex formation processes of the reference compound 8-hydroxyquinoline (Q-1) and three related Mannich bases to reveal possible correlations with biological activity. The studied derivatives harbor a CH2-N moiety at position 7 linked to morpholine (Q-2), piperidine (Q-3), and chlorine and fluorobenzylamino (Q-4) substituents. Solid phase structures of Q-3, Q-4·HCl·H2O, [(Cu(HQ-2)2)2]·(CH3OH)2·Cl4·(H2O)2, [Cu(Q-3)2]·Cl2 and [Cu(HQ-4)2(CH3OH)]·ZnCl4·CH3OH were characterized by single-crystal X-ray diffraction analysis. In addition, the redox properties of the copper and iron complexes were studied by cyclic voltammetry, and the direct reaction with physiologically relevant reductants (glutathione and ascorbic acid) was monitored. In vitro cytotoxicity studies conducted with the human uterine sarcoma MES-SA/Dx5 cell line reveal the significant cytotoxicity of Q-2, Q-3, and Q-4 in the sub- to low micromolar range (IC50 values 0.2-3.3 μM). Correlation analysis of the anticancer activity and the metal binding properties of the compound series indicates that, at physiological pH, weaker copper(ii) and iron(iii) binding results in elevated toxicity (e.g.Q4: pCu = 13.0, pFe = 6.8, IC50 = 0.2 μM vs.Q1: pCu = 15.1, pFe = 13.0 IC50 = 2.5 μM). Although the studied 8-hydroxyquinolines preferentially bind copper(ii) over iron(iii), the cyclic voltammetry data revealed that the more cytotoxic ligands preferentially stabilize the lower oxidation state of the metal ions. A linear relationship between the pKa (OH) and IC50 values of the studied 8-hydroxyquinolines was found. In summary, we identify Q-4 as a potent and selective anticancer candidate with significant toxicity in drug resistant cells.

Topics: Antineoplastic Agents; Ascorbic Acid; Cell Line, Tumor; Cell Survival; Coordination Complexes; Copper; Drug Resistance, Neoplasm; Female; Ferric Compounds; Glutathione; Humans; Inhibitory Concentration 50; Mannich Bases; Oxyquinoline; Sarcoma; Uterine Neoplasms

Uterine leiomyomas can be classified into molecularly distinct subtypes according to their genetic triggers: MED12 mutations, HMGA2 upregulation, or inactivation of FH. The aim of this study was to identify metabolites and metabolic pathways that are dysregulated in different subtypes of leiomyomas.. We performed global metabolomic profiling of 25 uterine leiomyomas and 17 corresponding myometrium specimens using liquid chromatography-tandem mass spectroscopy.. A total of 641 metabolites were detected. All leiomyomas displayed reduced homocarnosine and haeme metabolite levels. We identified a clearly distinct metabolomic profile for leiomyomas of the FH subtype, characterised by metabolic alterations in the tricarboxylic acid cycle and pentose phosphate pathways, and increased levels of multiple lipids and amino acids. Several metabolites were uniquely elevated in leiomyomas of the FH subtype, including N6-succinyladenosine and argininosuccinate, serving as potential biomarkers for FH deficiency. In contrast, leiomyomas of the MED12 subtype displayed reduced levels of vitamin A, multiple membrane lipids and amino acids, and dysregulation of vitamin C metabolism, a finding which was also compatible with gene expression data.. The study reveals the metabolomic heterogeneity of leiomyomas and provides the requisite framework for strategies designed to target metabolic alterations promoting the growth of these prevalent tumours.

Topics: Adenosine; Amino Acids; Argininosuccinic Acid; Ascorbic Acid; Citric Acid Cycle; Female; Fumarate Hydratase; HMGA2 Protein; Humans; Leiomyoma; Lipid Metabolism; Mediator Complex; Metabolic Networks and Pathways; Metabolome; Pentose Phosphate Pathway; Uterine Neoplasms; Vitamin A

The authors here report a case of an infertile woman with diffuse leiomyomatosis of the uterus, which is a rare benign pathological condition in which the myometrium is occupied by innumerable small fibroid nodules. Due to the progressive abdominal distension of the patient and the desire for pregnancy of the couple, myomectomy was performed as a primary treatment. Urgent relaparotomy was required for hematoma debridement on the following day. Despite the evidence of the follicular growth and cyclic ovarian steroid secretion, the patient had postoperative endometrial thinning that was unresponsive to hormone replacement therapy. Supplementation of oral tocopherol nicotinate/vitamin E and ascorbic acid/vitamin C was effective for immediate recovery of withdrawal bleeding and gradual gain of endometrial thickness. The patient had a successful pregnancy in an in vitro fertilization-embryo transfer program and gave a birth to a healthy baby.

Topics: Adult; Ascorbic Acid; Dietary Supplements; Endometrium; Female; Fertility Preservation; Humans; Infertility, Female; Leiomyomatosis; Pregnancy; Uterine Myomectomy; Uterine Neoplasms; Vitamin E; Vitamins

A specific nutrient mixture (NM) containing lysine, proline, ascorbic acid and green tea extract has demonstrated a broad spectrum of antitumor activity against a number of cancer cell lines. In this study, our main objective was to investigate the comparative effects of NM on anticancer parameters, such as cytotoxicity, matrix metalloproteinase (MMP) secretion and Matrigel invasion in the human uterine sarcoma drug-resistant MES-SA/Dx5 and the drug-sensitive MES-SA cell lines. In addition we studied the effects of NM on P-glycoprotein (Pgp) on these cell lines. Cell proliferation was evaluated by MTT assay, MMPs by gelatinase zymography, invasion through Matrigel, morphology by H&E and Pgp expression by Western blot analysis and immunodetection using FITC-conjugated antibody and rhodamine 123 (Rh123) accumulation and efflux assays. NM exhibited antiproliferative effects on MES-SA/Dx5, by 20% at 50 and 100 µg/ml and by 36, 40 and 48% at 250, 500 and 1,000 µg/ml, respectively. By contrast, NM treatment of MES-SA cells resulted in significantly increased cytotoxicity: 40, 46, 65 and 72% at 50, 100, 500 and 1,000 µg/ml, respectively. In both cell lines, zymography demonstrated a band corresponding to MMP-2 in normal cells and MMP-9 with phorbol 12-myristate 13-acetate treatment. The two MMPs showed dose-response inhibition by NM. As shown by Western blot analysis and immunodetection, NM treatment resulted in a dose-dependent decrease in Pgp expression in the MES-SA/Dx5 cell line. The MES-SA cell line does not exhibit Pgp. NM enhanced the accumulation and efflux of the Pgp substrate, Rh123, in the MES-SA/Dx5 uterine sarcoma cell line but not in the drug-sensitive cell line, MES-SA. Therefore, it can be concluded that NM demonstrates potent anticancer effects in both the drug-resistant and sensitive cell lines and modulates Pgp, suggesting its potential therapeutic effects in drug-resistant as well as sensitive cancers.

Topics: Antineoplastic Agents; Ascorbic Acid; ATP Binding Cassette Transporter, Subfamily B, Member 1; Blotting, Western; Cell Line, Tumor; Cell Movement; Cell Proliferation; Cell Survival; Drug Resistance, Multiple; Drug Resistance, Neoplasm; Female; Food; Humans; Lysine; Plant Extracts; Proline; Sarcoma; Tea; Uterine Neoplasms

Reduced vitamin C [ascorbic acid (AA)], which is taken up into cells by sodium-dependent vitamin C transporter (SVCT) 1 and 2, is believed to be important for hormone synthesis, but its role in generating placental steroids needed to maintain pregnancy and fetal development is not clear. To determine the steroidogenic effect of AA and the role of SVCT2 in AA-induced steroidogenesis, we tested the effects of AA treatment and SVCT2 knockdown on steroidogenesis in human choriocarcinoma cell lines. AA treatment of JEG-3, BeWo, and JAR cells for 48-h dose dependently increased progesterone and estradiol levels. In JEG-3 cells, AA increased the mRNA expression of P450 cholesterol side-chain cleavage enzyme, 3beta-hydroxysteroid dehydrogenase type 1, and aromatase, key enzymes for steroidogenesis. Stable knockdown of SVCT2 in JEG-3 cells by retrovirally mediated RNA interference decreased the maximal velocity of AA uptake by approximately 50%, but apparent affinity values were not affected. SVCT2 knockdown in JEG-3 cells significantly suppressed the AA-induced mRNA expression of placental P450 cholesterol side-chain cleavage enzyme, 3beta-hydroxysteroid dehydrogenase type 1, and aromatase. This suppression of the AA-induced mRNA expression of steroidogenic enzymes subsequently decreased progesterone and estradiol production. In addition, inhibition of MAPK kinase-ERK signaling, which is a major pathway for AA-regulated gene expression, failed to affect AA-induced steroidogenesis. Our observations indicate that SVCT2-mediated AA uptake into cells is necessary for AA-induced steroidogenesis in human choriocarcinoma cell, but MAPK kinase-ERK signaling is not involved in AA-induced steroidogenesis.

Topics: 3-Hydroxysteroid Dehydrogenases; Aromatase; Ascorbic Acid; Cholesterol Side-Chain Cleavage Enzyme; Choriocarcinoma; Estradiol; Female; Gene Expression Regulation, Enzymologic; Gene Expression Regulation, Neoplastic; Humans; Mitogen-Activated Protein Kinase Kinases; Models, Biological; Organic Anion Transporters, Sodium-Dependent; Pregnancy; Progesterone; RNA, Messenger; RNA, Small Interfering; Sodium-Coupled Vitamin C Transporters; Steroids; Symporters; Tumor Cells, Cultured; Uterine Neoplasms

To examine the mechanism of radiation enhancement by motexafin gadolinium (Gd-Tex) in vitro.. Oxidation of ascorbate and NADPH by Gd-Tex was evaluated in a neutral buffer. Growth inhibition of human uterine cancer cell line MES-SA was measured using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) dye. Clonogenic assays were used to measure radiation response in MES-SA, A549 human lung carcinoma, E89, a CHO cell line variant deficient in glucose-6-phosphate dehydrogenase activity, and murine lymphoma cell lines LYAR and LYAS.. Gd-Tex catalyzed the oxidation of NADPH and ascorbate under aerobic conditions, forming hydrogen peroxide. Decreased viability was observed in MES-SA cells incubated with Gd-Tex in media containing NADPH or ascorbate. Gd-Tex and ascorbate increased fluorescence in dichlorofluorescin acetate-treated cultures. Synergistic effects on the aerobic radiation response in MES-SA and A549 were seen using Gd-Tex in combination with L-buthionine-(S,R)-sulfoximine (BSO). Incubation with Gd-Tex in the presence of ascorbate increased the aerobic radiation response of E89 and the apoptosis-sensitive B-cell line (LYAS).. Gd-Tex sensitizes cells to ionizing radiation by increasing oxidative stress as a consequence of futile redox cycling. Optimization of the concentration of ascorbate (or other reducing species) may be required when evaluating Gd-Tex activity in vitro.

Topics: Animals; Antineoplastic Agents; Ascorbic Acid; CHO Cells; Cricetinae; Female; Humans; Hydrogen Peroxide; Metalloporphyrins; NADP; Oxidation-Reduction; Reactive Oxygen Species; Tumor Cells, Cultured; Uterine Neoplasms

The goal of this study was to evaluate whether endothelial dysfunction associated with acute estrogen deprivation is caused by an alteration in the L-arginine-nitric oxide (NO) pathway and oxidative stress. Methods and Results-In 26 healthy women (age, 45.7+/-5.4 years) and 18 fertile women with leiomyoma (age, 44.5+/-5.1 years), we studied forearm blood flow (strain-gauge plethysmography) changes induced by intrabrachial acetylcholine (0. 15, 0.45, 1.5, 4.5, or 15 microgram. 100 mL(-1). min(-1)) or sodium nitroprusside (1, 2, or 4 microgram. 100 mL(-1). min(-1)), an endothelium-dependent or -independent vasodilator, respectively. The NO pathway was evaluated by repeating acetylcholine during L-arginine (200 microgram. 100 mL(-1). min(-1); 13 control subjects and 9 patients) or N(G)-monomethyl-L-arginine (L-NMMA; 100 microgram. 100 mL(-1). min(-1); 13 control subjects and 9 patients); production of cyclooxygenase-derived vasoconstrictors was assessed by repeating acetylcholine during indomethacin (50 microgram. 100 mL(-1). min(-1); 13 control subjects and 9 patients) or vitamin C (8 mg. 100 mL(-1). min(-1); 13 control subjects and 9 patients). Patients repeated the study within 1 month after ovariectomy and again after 3 months of estrogen replacement therapy (ERT; 17 beta-estradiol TTS, 50 microgram/d). Basally, vasodilation to acetylcholine was potentiated and inhibited by L-arginine and L-NMMA, respectively (P<0.05), but was unaffected by indomethacin or vitamin C. After ovariectomy, the modulating effect of L-arginine and L-NMMA disappeared, whereas indomethacin and vitamin C potentiated the response to acetylcholine (P<0.05). ERT restored L-arginine and L-NMMA effects on vasodilation to acetylcholine but prevented the potentiation caused by indomethacin or vitamin C. Response to sodium nitroprusside was unaffected by either ovariectomy or ERT.. Endothelial dysfunction secondary to acute endogenous estrogen deprivation is caused by reduced NO availability. Cyclooxygenase-dependent production of oxidative stress could be responsible for this alteration.

Topics: Acetylcholine; Adult; Arginine; Ascorbic Acid; Blood Pressure; Cardiovascular Agents; Endothelium, Vascular; Enzyme Inhibitors; Estrogen Replacement Therapy; Estrogens; Female; Forearm; Humans; Indomethacin; Leiomyoma; Middle Aged; omega-N-Methylarginine; Ovariectomy; Postoperative Period; Reference Values; Regional Blood Flow; Uterine Neoplasms; Vasodilation; Vasodilator Agents

We report here on the cloning and functional characterization of human SVCT2, a sodium-dependent vitamin C (ascorbate) transporter. The hSVCT2 cDNA obtained from a human placental choriocarcinoma cell cDNA library, codes for a protein of 650 amino acids with a predicted molecular mass of 70 kDa. At the level of amino acid sequence, the human SVCT2 exhibits 95% identity to its rat homolog. When functionally expressed in mammalian cells, hSVCT2 induces the transport of ascorbic acid. The transport process induced by hSVCT2 is Na(+)-dependent and is specific for ascorbate. The Michaelis-Menton constant (K(t)) for the transport of ascorbate in cDNA-transfected cells is 69 +/- 5 microM. The relationship between the cDNA-specific uptake rate of ascorbate and Na(+) concentration is sigmoidal with a Na(+):ascorbate stoichiometry of 2:1. Northern blot analysis shows that SVCT2-specific transcripts are present in heart, brain, placenta, and liver and is absent in lung and skeletal muscle. The size of the principal transcript is approximately 7.5 kb.

Topics: Amino Acid Sequence; Animals; Ascorbic Acid; Base Sequence; Biological Transport; Cell Line; Choriocarcinoma; Cloning, Molecular; Female; Gene Library; Humans; Kinetics; Molecular Sequence Data; Organic Anion Transporters, Sodium-Dependent; Pregnancy; Proteins; Rats; Recombinant Proteins; Sodium; Sodium-Coupled Vitamin C Transporters; Substrate Specificity; Symporters; Transfection; Tumor Cells, Cultured; Uterine Neoplasms

We investigated the transport pathways available for the uptake of vitamin C in the human placental choriocarcinoma cell line, JAR. These cells were found to possess the capacity to accumulate the vitamin when presented either in the oxidized form (dehydroascorbic acid) or in the reduced form (ascorbate). Dithiothreitol and 5,5'-dithiobis(2-nitrobenzoic acid) were used to maintain vitamin C as ascorbate and dehydroascorbic acid, respectively. The uptake of these two forms of vitamin C in JAR cells was found to occur by different mechanisms. The uptake of the dehydroascorbic acid was Na(+)-independent and was mediated by facilitative glucose transporters as evidenced from the inhibition of the uptake process by glucose. On the other hand, the uptake of ascorbate was Na(+)-dependent and was not sensitive to inhibition by glucose. Substitution of Na+ with other monovalent cations abolished the uptake of ascorbate completely. The uptake process was, however, not influenced by anions. Kinetic analysis indicated the presence of a single saturable transport system for ascorbate with a Michaelis-Menten constant of 22 +/- 1 microM. The dependence of the uptake rare of ascorbate on Na+ concentration exhibited sigmoidal kinetics, suggesting interaction of more than one Na+ ion with the transporter. The Hill coefficient for the Na+ interaction was 2, indicating that the Na(+)-dependent ascorbate transport is electrogenic. The Na(+)-dependent stimulation of ascorbate uptake was primarily due to an increase in the affinity of the transporter for ascorbate in the presence of Na+. It is concluded that the JAR placental trophoblast cell line expresses two different transport systems for vitamin C: one for the reduced form of the vitamin ascorbate; and the other for the oxidized form of the vitamin dehydroascorbic acid.

Topics: Ascorbic Acid; Biological Transport; Carrier Proteins; Choriocarcinoma; Dithionitrobenzoic Acid; Dithiothreitol; Female; Humans; Placenta; Sodium; Tumor Cells, Cultured; Uterine Neoplasms

CBA female mice treated with 1,2-dimethylhydrazine (DMH) alone or in combination with oestradiol dipropionate (EP) or ascorbic acid (AA) developed, as expected, a high incidence of uterine sarcomas. In addition, sarcomatous lesions at unusual sites (mainly in the forestomach) were evident. The incidence of sarcomatous lesions at other sites was 53/220 in mice having uterine sarcomas and 0/186 in mice treated with DMH but without uterine sarcomas. The difference between the two groups was highly statistically significant (P < 0.001) and demonstrates non-coincidental association of the above sarcomatous lesions with uterine sarcomas. Uterine sarcomas which presented in association with lesions at other sites were of a larger size than those found in isolation, and the difference in weights in three out of four groups was statistically significant (P = 0.008, 0.035 and 0.011). Histologically, sarcomatous lesions were similar in structure to those of uterine sarcomas, i.e. were of a fibroblastic-histiocytic nature with admixture of giant cells. On the basis of the above data the sarcomatous lesions described appear to represent uterine sarcoma metastases rather than independent primary tumours. AA did not have any influence on carcinogenesis induced by DMH alone but inhibited the growth of uterine sarcomas (whether or not they were associated with other sarcomatous lesions) induced by DMH combined with oestradiol dipropionate.

Topics: 1,2-Dimethylhydrazine; Animals; Ascorbic Acid; Carcinogens; Colonic Neoplasms; Dimethylhydrazines; Estradiol; Female; Incidence; Mice; Mice, Inbred CBA; Mutagens; Sarcoma; Stomach Neoplasms; Uterine Neoplasms

Topics: Animals; Ascorbic Acid; Carcinogens; Dimethylhydrazines; Estradiol; Female; Mice; Mice, Inbred CBA; Neoplasm Metastasis; Sarcoma, Experimental; Uterine Neoplasms

Administration of estradiol-dipropionate (EP) after the cessation of 1,2-dimethylhydrazine (DMH) treatment increased the incidence of uterine sarcomas in CBA mice from 32.5 (DMH alone) to 62.5%. Ascorbic acid (AA) (0.3% in drinking water) given simultaneously with EP decreased the tumour incidence to 35%. Sodium ascorbate did not exert an inhibiting effect. AA inhibited the increase of uterine weight produced in mice by EP and did not influence the growth of mouse transplantable uterine sarcomas. The mechanisms of the antiestrogenic effects of AA are discussed.

Topics: 1,2-Dimethylhydrazine; Animals; Ascorbic Acid; Carcinogens; Dimethylhydrazines; Drug Antagonism; Estradiol; Female; Life Tables; Mice; Mice, Inbred CBA; Organ Size; Sarcoma, Experimental; Uterine Neoplasms

The administration of estradiol propionate after the discontinuation of 1,2-dimethylhydrazine (DMH) treatment increased the incidence of uterine sarcoma in CBA mice from 32.5 (DMH alone) to 62.5%. The addition of the ascorbic acid (0.3% solution in drinking water) to estradiol propionate was followed by a decrease in the tumor incidence to 35%, i. e. the acid levelled the promoting effect of estradiol propionate almost completely. Sodium ascorbate did not share that effect. Mechanisms underlying the antiestrogenic effect of the ascorbic acid are discussed.

Topics: 1,2-Dimethylhydrazine; Animals; Ascorbic Acid; Carcinogens; Dimethylhydrazines; Drug Interactions; Drug Screening Assays, Antitumor; Estradiol; Estrogen Antagonists; Female; Mice; Mice, Inbred CBA; Sarcoma, Experimental; Uterine Neoplasms

The effects of sodium ascorbate (vitamin C) and 2-methyl-1,4-naphthoquinone (vitamin K3) administered separately or in combination on the in vitro cultured human neoplastic cell lines MCF-7 (breast carcinoma), KB (oral epidermoid carcinoma), and AN3-CA (endometrial adenocarcinoma) have been examined. When given separately, vitamin C or K3 had a growth inhibiting action only at high concentrations (5.10(3) mumol/1 and 10(5) nmol/l, respectively). Combined administration of both vitamins demonstrated a synergistic inhibition of cell growth at 10 to 50 times lower concentrations. At this level separately given vitamins are not toxic. The sensitivity to this treatment was somewhat different in the three cell lines, being slightly higher for KB line. This tumor cell growth inhibitory effect was completely suppressed by the addition of catalase to the culture medium containing vitamins C and K3, suggesting an excessive production of hydrogen peroxide as being implied in mechanisms responsible for the above-mentioned effects.

Topics: Adenocarcinoma; Ascorbic Acid; Breast Neoplasms; Carcinoma, Squamous Cell; Catalase; Cell Division; Drug Synergism; Female; Humans; Mouth Neoplasms; Tumor Cells, Cultured; Uterine Neoplasms; Vitamin K

Administration of ascorbic acid (0.3% in drinking water) inhibited the promoting effect of estradiol dipropionate on the 1,2-dimethylhydrazine-induced uterine sarcomogenesis in CBA mice. However administration of sodium ascorbate intensified the promoting effect of estradiol on the uterine sarcomogenesis, as evidenced by the shortening of the periods of tumour incidence.

Topics: 1,2-Dimethylhydrazine; Animals; Ascorbic Acid; Cocarcinogenesis; Dimethylhydrazines; Drug Synergism; Female; Methylhydrazines; Mice; Mice, Inbred CBA; Sarcoma, Experimental; Uterine Neoplasms

Administration of ascorbic acid (0.3, 0.75 or 1.5%) in drinking water started after the treatment of female CBA mice with 1,2-dimethylhydrazine and estradiol-dipropionate inhibited the growth of uterine sarcomas. The inhibitory effect depended upon dosage to some extent. When administered together with estradiol-dipropionate to intact mice, ascorbic acid arrested uterine growth associated with estrogen treatment.

Topics: 1,2-Dimethylhydrazine; Animals; Ascorbic Acid; Body Weight; Dimethylhydrazines; Estradiol; Estrogen Antagonists; Female; Mice; Mice, Inbred CBA; Organ Size; Sarcoma, Experimental; Uterine Neoplasms; Uterus

L-Ascorbic acid inhibits the growth of mouse neuroblastoma and human endometrial carcinoma cells at concentrations greater than 100 microM. Under the same concentrations used in cell culture study, normal human lung fibroblasts show less sensitivity to the antiproliferative effect of ascorbate than tumor cell lines. The antitumor activity of ascorbate can be greatly potentiated by the combination with copper ions or copper chelates. The exposure of normal and tumor cells to the mixtures of ascorbate and copper chelates, especially Cu2+-o-phenanthroline and Cu2+-2,9-dimethyl-o-phenanthroline complexes, resulted in the killing of a large proportion of cell populations whereas the organic ligand portion of metal complexes was much less toxic. These copper chelates in combination with ascorbate showed different degrees of DNA-scission activities which could not be correlated with their cytotoxicities in the cell culture study. It is suggested that the primary targets of these antiproliferative agents may be on the biological sites such as cell membrane other than DNA in the nucleus which has been commonly assumed as the critical target for most free radical-generating antitumor drugs.

Topics: Animals; Ascorbic Acid; Bacteriophage lambda; Cell Division; Cell Line; Chelating Agents; Copper; DNA, Viral; Female; Humans; Kinetics; Lung; Mice; Neuroblastoma; Uterine Neoplasms

The influence of external abdominal irradiation and cytostatic therapy on the vitamin status was studied in patients with cancer of the uterus, bladder or prostate and in patients with malignant lymphoma. It was found that the vitamin status of these patients at the beginning of therapy in general was adequate, though vitamin A and vitamin D levels were reduced. During radiotherapy decreases of vitamin E, vitamin C, vitamin B12 and folic acid levels were observed. Chemotherapy caused a decrease of the folic acid levels after a few months. No clinical symptoms of vitamin deficiency were observed.

Topics: Ascorbic Acid; Calcifediol; Female; Humans; Lymphoma; Male; Neoplasms; Prostatic Neoplasms; Urinary Bladder Neoplasms; Uterine Neoplasms; Vitamin A; Vitamin B 12; Vitamin E; Vitamins

The authors report the results of studies on the content of ascorbic acid, pyruvic acid and the activity of malate dehydrogenase decarboxylizing (MDHD) in cell nuclei of uterine fibromyoma, glandular hyperplasia of the endometrium with epithelial proliferation, common ovarian cyst and solid cancer. It was shown that due to the glycolysis inhibited respiration an oxidated form of ascorbic acid is absent in every case, whereas the MDHD activity is not manifested. The amount of a reduced form of ascorbic and pyruvic acid in benign tumors is at the control level, but in malignant growth these indices are markedly increased.

Topics: Ascorbic Acid; Carcinoma; Cell Nucleus; Decarboxylation; Endometrial Hyperplasia; Female; Humans; Hydroxy Acids; Keto Acids; Leiomyoma; Malate Dehydrogenase; Ovarian Cysts; Ovarian Neoplasms; Pyruvates; Uterine Neoplasms

Topics: Acidosis; Adult; Aged; Ascorbic Acid; Female; Glucose; Humans; Insulin; Intestinal Neoplasms; Lung Neoplasms; Male; Middle Aged; Ovarian Neoplasms; Premedication; Pyridoxine; Stomach Neoplasms; Thiamine; Thiamine Pyrophosphate; Uterine Neoplasms

Topics: Androstanes; Androstenols; Ascorbic Acid; Cobalt Isotopes; Convalescence; Cystine; Drug Synergism; Female; Genital Neoplasms, Female; Humans; Ovarian Neoplasms; Pantothenic Acid; Pyridoxine; Radioisotope Teletherapy; Thiamine; Uterine Cervical Neoplasms; Uterine Neoplasms; Vitamin A; Vitamin B 12; Vitamin B Complex

Topics: Adenoma, Chromophobe; Ascorbic Acid; Breast Neoplasms; Choriocarcinoma; Chorionic Gonadotropin; Female; Hemagglutination Inhibition Tests; Humans; Immune Sera; Luteinizing Hormone; Menopause; Middle Aged; Pituitary Neoplasms; Pregnancy; Uterine Neoplasms

Topics: Animals; Ascorbic Acid; Biological Assay; Blood; Castration; Chorionic Gonadotropin; Female; Gonadotropins, Equine; Humans; Luteinizing Hormone; Menstruation; Ovary; Rats; Uterine Cervical Neoplasms; Uterine Neoplasms

Topics: Adrenal Cortex; Adrenocorticotropic Hormone; Ascorbic Acid; Female; Humans; Leiomyoma; Urine; Uterine Neoplasms; Vitamins

Topics: Adrenocorticotropic Hormone; Ascorbic Acid; Female; Humans; Leiomyoma; Urine; Uterine Neoplasms

Topics: Androgens; Ascorbic Acid; Female; Humans; Leiomyoma; Pregnancy; Pregnancy Complications; Testosterone; Uterine Neoplasms; Vitamin E

Topics: Ascorbic Acid; Female; Humans; Neoplasms; Uterine Neoplasms; Vitamin A; Vitamins

Topics: Ascorbic Acid; Body Fluids; Female; Humans; Leiomyoma; Uterine Neoplasms; Vitamins