ascorbic-acid and Urogenital-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

Topics: Adolescent; Adult; Age Factors; Amenorrhea; Animals; Ascorbic Acid; Biological Assay; Clomiphene; Drug Synergism; Estrogens; Female; Follicle Stimulating Hormone; Gonadotropins; Gonadotropins, Pituitary; Humans; Hypogonadism; Luteinizing Hormone; Male; Menopause; Methods; Middle Aged; Ovarian Cysts; Ovary; Ovulation; Progestins; Prolactin; Rats; Urogenital Neoplasms

DNA 5-hydroxymethylcytosine (5hmC) is produced by dynamic 5mC oxidation process contributing to tissue specification, and loss of 5hmC has been reported in multiple cancers including genitourinary cancers. However, 5hmC is also cell-type specific, and its variability may exist between differentiated tumor cells and cancer stem cells. Thus, cancer-associated changes in 5hmC may be contributed by distinct sets of tumor cells within the tumor tissues.. Here, we applied a sensitive immunoprecipitation-based method (hMeDIP-seq) to analyze 5hmC changes during genitourinary carcinogenesis (including prostate, urothelial and kidney). We confirmed the tissue-specific distribution of 5hmC in genitourinary tissues and identified regional gain and global loss of 5hmC coexisting in genitourinary cancers. The genes with gain of 5hmC during tumorigenesis were functionally enriched in regulating stemness and hypoxia, whereas were associated with poor clinical prognosis irrespective of their differences in tumor type. We identified that gain of 5hmC occurred in soft fibrin gel-induced 3D tumor spheres with a tumor-repopulating phenotype in two prostate cancer cell lines, 22RV1 and PC3, compared with conventional two-dimensional (2D) rigid dishes. Then, we defined a malignant signature derived from the differentially hydroxymethylated regions affected genes of cancer stem-like cells, which could predict a worse clinical outcome and identified phenotypically malignant populations of cells from prostate cancer tumors. Notably, an oxidation-resistant vitamin C derivative, ascorbyl phosphate magnesium, restored 5hmC and killed the cancer stem cell-like cells leading to apoptosis in prostate cancer cell lines.. Collectively, our study dissects the regional gain of 5hmC in maintaining cancer stem-like cells and related to poor prognosis, which provides proof of concept for an epigenetic differentiation therapy with vitamin C by 5hmC reprogramming.

Topics: 5-Methylcytosine; Ascorbic Acid; Carcinogenesis; DNA; DNA Methylation; Fibrin; Humans; Magnesium; Male; Phosphates; Prostatic Neoplasms; Urogenital Neoplasms

A micro-tetrazolium assay was employed to evaluate vitamin C (VC), vitamin K3 (VK3) and vitamin C/vitamin K3 combinations (VC/VK3) for their antitumor activity against eight human urologic tumor cell lines. While the individual vitamins exhibited antitumor activity at high concentrations, co-administration of the vitamins in a VC : VK3 ratio of 100 : 1 potentiated antitumor activity 4- to 61-fold even when exposure times were as short as 1 hour. Administration of exogenous catalase destroyed the antitumor activity of the vitamins and suggested that hydrogen peroxide and perhaps other reactive oxygen species were involved in the antitumor mechanism of these vitamins. Electron micrographs taken in a previous study demonstrated that vitamin treatment damaged mitochondria and may have impaired ATP synthesis. Analysis of cellular ATP and thiol levels as well as DNA and protein synthesis during the first five hours following a one hour VC/VK3 treatment, revealed: a transient increase in ATP production, a substantial decrease in DNA synthesis, an increase in protein synthesis and a decrease in thiol levels. These results suggested that redox cycling of the vitamin combination increased oxidative stress until it surpassed the reducing ability of the cellular thiols and cellular or genetic damage ensued.

Topics: Adenosine Triphosphate; Ascorbic Acid; DNA Replication; Drug Synergism; Humans; Microscopy, Electron; Reactive Oxygen Species; Sulfhydryl Compounds; Tumor Cells, Cultured; Urogenital Neoplasms; Vitamin K