ascorbic-acid and Laryngeal-Neoplasms

Ascorbic acid induces apoptosis, autophagy, and necrotic cell death in cancer cells. We investigated the mechanisms by which ascorbic acid induces death in laryngeal squamous cell carcinoma Hep2 cells. Ascorbic acid markedly reduced cell viability and induced death without caspase activation and an increase in cytochrome c. Hep2 cells exposed to ascorbic acid exhibited membrane rupture and swelling, the morphological characteristics of necrotic cell death. The generation of reactive oxygen species (ROS) was increased in Hep2 cells treated with ascorbic acid, and pretreatment with N-acetylcysteine blocked ascorbic acid-induced cell death. Ascorbic acid also stimulated protein kinase C (PKC) signaling, especially PKC α/β activation, and subsequently increased cytosolic calcium levels. However, ascorbic acid-induced necrotic cell death was inhibited by Ro-31-8425 (PKC inhibitor) and BAPTA-AM (cytosolic calcium-selective chelator). ROS scavenger NAC inhibited PKC activation induced by ascorbic acid and Ro-31-8425 suppressed the level of cytosolic calcium increased by ascorbic acid, indicating that ROS is represented as an upstream signal of PKC pathway and PKC activation leads to the release of calcium into the cytosol, which ultimately regulates the induction of necrosis in ascorbic acid-treated Hep2 cells. These data demonstrate that ascorbic acid induces necrotic cell death through ROS generation, PKC activation, and cytosolic calcium signaling in Hep2 cells. J. Cell. Physiol. 232: 417-425, 2017. © 2016 Wiley Periodicals, Inc.

Topics: Apoptosis; Ascorbic Acid; Calcium; Calcium Signaling; Carcinoma, Squamous Cell; Cell Line, Tumor; Enzyme Activation; Humans; Laryngeal Neoplasms; Necrosis; Protein Kinase C; Reactive Oxygen Species

Head and neck cancer (HNC) is the seventh most-common type of cancer worldwide. Evidence regarding the potential protective effect of vitamins and carotenoids on HNC is limited and mostly based on case-control studies.. We evaluated the association of intake of dietary vitamins C and E (including supplementation) and the most-common carotenoids (α-carotene, β-carotene, lutein plus zeaxanthin, lycopene, and β-cryptoxanthin) and risk of HNC and HNC subtypes in a large prospective study.. The Netherlands Cohort Study included 120,852 participants. For efficiency reasons, a case-cohort design was used. At baseline in 1986, participants completed a food-frequency questionnaire. A subcohort was randomly selected from the total cohort. After 20.3 y of follow-up, 3898 subcohort members and 415 HNC cases [131 oral cavity cancer (OCCs), 88 oro-/hypopharyngeal cancer (OHPs), and 193 laryngeal cancer cases] were available for analysis. Rate ratios and 95% CIs for highest (quartile 4) compared with lowest (quartile 1) quartiles of vitamin and carotenoid intake were estimated by using the Cox proportional hazards model.. A strong inverse association was shown between vitamin C and HNC overall (multivariable-adjusted rate ratio for quartile 4 compared with quartile 1: 0.39; 95% CI: 0.23, 0.66; P-trend < 0.001), OCC (multivariable-adjusted rate ratio for quartile 4 compared with quartile 1: 0.35; 95% CI: 0.16, 0.77; P-trend < 0.05), and OHPC (multivariable-adjusted rate ratio for quartile 4 compared with quartile 1: 0.29; 95% CI: 0.12, 0.67; P-trend < 0.01). No statistically significant results were shown for vitamin E, α-carotene, β-carotene, lycopene, and lutein plus zeaxanthin. The association of vitamin E and HNC was modified by alcohol status (P-interaction = 0.003) with lower risks in alcohol abstainers.. With this study, we show an inverse association between intake of vitamin C and the incidence of HNC and HNC-subtypes. Future research is recommended to investigate the underlying mechanisms and to confirm our results, which may be promising for the prevention of HNC.

Topics: Aged; Antioxidants; Ascorbic Acid; Carotenoids; Case-Control Studies; Cohort Studies; Diet; Dietary Supplements; Female; Follow-Up Studies; Head and Neck Neoplasms; Humans; Hypopharyngeal Neoplasms; Incidence; Laryngeal Neoplasms; Male; Middle Aged; Mouth Neoplasms; Netherlands; Oropharyngeal Neoplasms; Prospective Studies; Registries; Risk Factors; Vitamin E

Effects of ascorbic acid on calcium homeostasis of human laryngeal carcinoma cells were studied. Intracellular concentration of free calcium and intracellular pH were measured by fluorescent analysis. Ascorbic acid in concentrations of 3-10 mM caused pH drop and sharply increased concentrations of free Ca ions in HEp-2 cells. Intracellular concentration of free Ca ions resulted from Ca ion release from the thapsigargin-sensitive Ca depots.

Topics: Antioxidants; Ascorbic Acid; Calcium; Calcium Signaling; Carcinoma; Cell Line, Tumor; Dose-Response Relationship, Drug; Enzyme Inhibitors; Extracellular Space; Fluorescence; Humans; Hydrogen Peroxide; Hydrogen-Ion Concentration; Intracellular Space; Laryngeal Neoplasms; Oxidants; Thapsigargin; Time Factors

Topics: Alcohol Drinking; Ascorbic Acid; Diet; Humans; Hypopharyngeal Neoplasms; Laryngeal Neoplasms; Smoking; Vegetables; Vitamins

Little information is available on the role of tobacco, alcohol and diet in the survival of upper aero digestive cancers. Our study analysed the survival of 931 laryngeal and hypopharyngeal cancer patients, enrolled in a population based case-control study conducted at 5 centres in southeast Europe during 1979-1982. Age at the time of diagnosis and site of origin of tumour were observed to be predictors of the survival. Cigarette smoking, and to a limited extent alcohol drinking, before the diagnosis of tumour seem to influence the overall survival whereas high intakes of vegetables and vitamin C were observed to favourably affect the prognosis. For mortality from upper aerodigestive cancer protective effects of high intakes of vegetables, fibres and vitamin C were observed. Our results support the hypothesis that there is a role for dietary intervention to improve survival of laryngeal and hypopharyngeal cancer patients.

Topics: Aged; Alcohol Drinking; Ascorbic Acid; Case-Control Studies; Diet; Dietary Fiber; Europe; Female; Humans; Hypopharyngeal Neoplasms; Laryngeal Neoplasms; Life Style; Male; Middle Aged; Prognosis; Proportional Hazards Models; Risk Factors; Smoking; Survival Rate; Vegetables

Incubation of human laryngeal epidermoid carcinoma HEp-2 cells with hydroxocobalamin (vitamin B12b) and ascorbic acid (vitamin C) for 1 h initiated oxidative stress accompanied by damage to mitochondria and increase in intracellular oxidative activity. Studies of the kinetics of these processes showed that the increase in intracellular H2O2 activity and mitochondrial damage are more likely a result, but not the cause of cell apoptosis during the first hour of their incubation with vitamins B12b and C.

Topics: Ascorbic Acid; Calcium; Cell Death; Cell Line, Tumor; Fluoresceins; Fluorescent Dyes; Humans; Hydrogen Peroxide; Hydroxocobalamin; Kinetics; Laryngeal Neoplasms; Membrane Potentials; Mitochondria; Oxidative Stress; Spectrometry, Fluorescence; Time Factors; Vitamin B 12

The confluence-dependent resistance of human larynx carcinoma HEp-2 cells to hydrogen peroxide and a new antitumor drug based on the combination of vitamins C and B12b was studied. It was found that this resistance in growing cells is suppressed by the disruption of intercellular contacts by EGTA and is related neither to the activity of P-glycoprotein nor to the content of intracellular glutathione and the activities of glutathione S-transferases, glutathione peroxidase and glutathionine reductase. Here we showed that the level of expression of the small heat shock protein hsp27, which is known to protect cells from a variety of stresses associated with apoptosis, in growing confluent cells both in the presence and absence of the vitamins B12b and C is much higher (about 20-25 times) than in non-confluent cells. Taken together, the results suggest that the confluence-dependent resistance of cells to the combination of vitamins C and B12b and to hydrogen peroxide is mediated by hsp27 overexpression, which is activated via cell-cell adhesion.

Topics: Antineoplastic Combined Chemotherapy Protocols; Ascorbic Acid; ATP Binding Cassette Transporter, Subfamily B, Member 1; Carcinoma; Cell Adhesion; Cell Communication; Cell Culture Techniques; Cell Division; Drug Resistance, Neoplasm; Egtazic Acid; Glutathione; Heat-Shock Proteins; HSP27 Heat-Shock Proteins; Humans; Hydrogen Peroxide; Hydroxocobalamin; Laryngeal Neoplasms; Molecular Chaperones; Neoplasm Proteins; Tumor Cells, Cultured

Cigarette smokers are known to have lower concentrations of circulating ascorbic acid than nonsmokers. In contrast, there is evidence that the extracellular fluid lining of the alveolus, which comes in close contact with cigarette smoke, and the alveolar macrophages of smokers are enriched with ascorbic acid. The clinical significance of these observations is unknown.. The authors measured the ascorbic acid concentrations and radiolabeled methyl incorporation (which is inversely related to the degree of DNA methylation in vivo) of paired samples of squamous cell carcinoma (SCC) and adjacent uninvolved mucosa of the lung and larynx (n = 22).. Cancerous tissues had significantly higher ascorbic acid concentrations (mean +/- standard deviation [SD, 485 +/- 77; median, 483 ng/mg protein) compared with their matched uninvolved tissues (mean +/- SD, 151 +/- 52; median, 72 ng/mg protein; P < 0.0001). The radiolabeled methyl incorporation was significantly higher in cancerous tissues (mean +/- SD, 31,419 +/- 2629; median, 31,416 counts per minute [CPM]/microg DNA) compared with their matched uninvolved tissues (mean +/- SD, 11,883 +/- 1567; median, 11,444 CPM/microg DNA; P < 0.0001). The Spearman correlation between ascorbic acid concentrations and radiolabeled methyl incorporation by DNA in SCCs was inverse and statistically significant (r = -0.58, P = 0.008), indicating a beneficial effect of accumulated ascorbic acid in global methylation of DNA. In the uninvolved tissues, this correlation was inverse but statistically not significant (r = -0.20, P =0.35).. Cancerous tissues of the lung and larynx demonstrated their ability to accumulate ascorbic acid. The accumulation of ascorbic acid by these tissues seemed to facilitate global methylation of DNA.

Topics: Aged; Aged, 80 and over; Ascorbic Acid; Carcinoma, Squamous Cell; DNA Methylation; Female; Humans; Laryngeal Neoplasms; Lung Neoplasms; Male; Middle Aged; Smoking

The combination of hydroxocobalamin (vitamin B12b) and ascorbic acid (vitamin C) can cause the death of tumor cells at the concentrations of the components at which they are nontoxic when administered separately. This cytotoxic action on epidermoid human larynx carcinoma cells HEp-2 in vitro is shown to be due to the hydrogen peroxide generated by the combination of vitamins B12b and C. The drop in the glutathione level preceding cell death was found to be the result of combined action of the vitamins. It is supposed that the induction of cell death by combined action of vitamins B12b and C is connected to the damage of the cell redox system.

Topics: Ascorbic Acid; Carcinoma, Squamous Cell; Cell Division; Drug Synergism; Glutathione; Humans; Hydrogen Peroxide; Laryngeal Neoplasms; Oxidation-Reduction; Tumor Cells, Cultured; Vitamin B 12

Interviews were carried out with 374 male patients at Roswell Park Memorial Institute with cancer of the larynx and 381 controls with diseases other than of the digestive or respiratory system and other than neoplasms. As have other investigators, the authors found a high risk associated with smoking as well as a risk associated with alcohol ingestion. In addition, the study found that males ingesting low amounts of vitamin A in their diet had approximately twice the risk of those ingesting large amounts. The same was true for vitamin C. All of these relationships were significant, and risk increased in dose-response fashion with decreases in ingestion of the above-mentioned dietary constituents. When the risks associated with vitamins A and C were examined controlling for smoking and drinking, the risk enhancement associated with low ingestion persisted. The findings on nutrients are consistent with results of studies on animals and tissue cultures. Nevertheless, the sparse epidemiologic replication, the difficulties with the methods, and the complexity of the field demand substantial further inquiry on these relationships.

Topics: Alcohol Drinking; Ascorbic Acid; Epidemiologic Methods; Humans; Laryngeal Neoplasms; Male; Risk; Smoking; Vegetables; Vitamin A

Previous work in this laboratory has thrown some light on the possible mechanism involved in the anti-tumour activity of ascorbic acid (AA). In order to elucidate this mechanism further, the present studies, involving the effect of AA on protein and RNA synthesis, were carried out. The results obtained in this investigation may support the hypothesis previously put forward for the action of AA on cell proliferation.

Topics: Ascorbic Acid; Carcinoma; Carcinoma, Squamous Cell; Cell Division; Cell Line; Humans; Laryngeal Neoplasms; Mouth Neoplasms; Neoplasm Proteins; RNA, Neoplasm