propylthiouracil and Neoplasms

The oxidative pentose phosphate pathway (PPP) contributes to tumour growth, but the precise contribution of 6-phosphogluconate dehydrogenase (6PGD), the third enzyme in this pathway, to tumorigenesis remains unclear. We found that suppression of 6PGD decreased lipogenesis and RNA biosynthesis and elevated ROS levels in cancer cells, attenuating cell proliferation and tumour growth. 6PGD-mediated production of ribulose-5-phosphate (Ru-5-P) inhibits AMPK activation by disrupting the active LKB1 complex, thereby activating acetyl-CoA carboxylase 1 and lipogenesis. Ru-5-P and NADPH are thought to be precursors in RNA biosynthesis and lipogenesis, respectively; thus, our findings provide an additional link between the oxidative PPP and lipogenesis through Ru-5-P-dependent inhibition of LKB1-AMPK signalling. Moreover, we identified and developed 6PGD inhibitors, physcion and its derivative S3, that effectively inhibited 6PGD, cancer cell proliferation and tumour growth in nude mice xenografts without obvious toxicity, suggesting that 6PGD could be an anticancer target.

Topics: AMP-Activated Protein Kinase Kinases; AMP-Activated Protein Kinases; Humans; Lipogenesis; Neoplasms; Oxidative Stress; Pentose Phosphate Pathway; Phosphogluconate Dehydrogenase; Protein Serine-Threonine Kinases; Ribulosephosphates; Signal Transduction

To collect and assess clinical reports of a putative relationship between thyroid state and the biology of cancers of various types.. A number of prospective case-control studies reviewed here have suggested that subclinical hyperthyroidism increases risk of certain solid tumors and that spontaneous hypothyroidism may delay onset or reduce aggressiveness of cancers. Small case studies have reached similar conclusions. A controlled prospective trial of induced hypothyroidism beneficially affected the course of glioblastoma. A context in which to interpret such findings is the recent description of a plasma membrane receptor for thyroid hormone on cancer cells and dividing tumor-associated endothelial cells.. Accumulating clinical evidence may justify new, broadly-based controlled studies in cancer patients of the possible contribution of thyroid hormone to tumor behavior.

Topics: Animals; Antithyroid Agents; Cell Proliferation; Female; Humans; Hyperthyroidism; Hypothyroidism; Integrin alphaVbeta3; Neoplasms; Propylthiouracil; Rats; Receptors, Thyroid Hormone; Risk Factors; Thyroid Hormones

Genetically mediated sensitivity to the bitter taste of phenylthiocarbamide (PTC) and 6-n-propylthiouracil (Prop) has long been associated with enhanced sensitivity to other sweet and bitter compounds. New studies suggest that tasters and supertasters of Prop may also differ from notasters in their taste preferences and in their patterns of food rejection and food acceptance. One question is whether the acceptability of bitter-tasting vegetables is influenced by Prop taster status. Cruciferous vegetables are among the major dietary sources of potentially chemoprotective agents in cancer control, and their consumption is reported to alter cancer risk. Strategies aimed at dietary change in individuals or groups should consider the role of genetic taste markers and their potential influences on food preferences and dietary habits.

Topics: Alcoholism; Food Preferences; Genetic Markers; Humans; Neoplasms; Nutritional Physiological Phenomena; Phenylthiourea; Propylthiouracil; Risk Factors; Taste; Vegetables

Topics: Animals; Antimetabolites; Antithyroid Agents; Carcinogens; Humans; Neoplasms; Propylthiouracil

Topics: Antithyroid Agents; Humans; Hyperthyroidism; Long-Acting Thyroid Stimulator; Methimazole; Neoplasms; Propylthiouracil; Thyroidectomy

Topics: Adenoma, Oxyphilic; Animals; Carcinoma; Iodine Isotopes; Mice; Neoplasms; Neoplasms, Experimental; Pathology; Propylthiouracil; Radiation Effects; Research; Thyroid Neoplasms; Thyrotropin; Transplantation, Homologous

Topics: Adolescent; Antithyroid Agents; Child; Drug Therapy; Humans; Hyperthyroidism; Iodine Isotopes; Neoplasms; Neoplasms, Radiation-Induced; Perchlorates; Propylthiouracil; Thyroid Neoplasms; Thyroidectomy; Toxicology

Topics: Blood Chemical Analysis; Chromatography; Geriatrics; Goiter; Hyperthyroidism; Iodine Isotopes; Monoiodotyrosine; Myxedema; Neoplasms; Propylthiouracil; Thiourea; Thyronines; Thyroxine; Tyrosine

Topics: Adenocarcinoma; Adolescent; Humans; Infertility; Iodine Isotopes; Lymphatic Metastasis; Neck Dissection; Neoplasm Metastasis; Neoplasms; Pathology; Propylthiouracil; Radiation Injuries; Surgical Procedures, Operative; Thyroid Function Tests; Thyroid Hormones; Thyroid Neoplasms; Thyroidectomy; Toxicology

Topics: Body Weight; Carcinogens; Guinea Pigs; Iodides; Iodine; Neoplasms; Neoplasms, Experimental; Pathology; Propylthiouracil; Research; Thyroid Neoplasms; Thyroiditis; Toxicology

Topics: Animals; Biological Assay; Blood Chemical Analysis; Neoplasms; Neoplasms, Experimental; Pharmacology; Poultry; Propylthiouracil; Rats; Research; Thyroid Neoplasms; Thyrotropin

Topics: Iodides; Neoplasms; Pituitary Diseases; Pituitary Gland; Propylthiouracil; Thiouracil; Thyroid Gland; Thyroid Neoplasms

Topics: Animals; Mice; Neoplasms; Neoplasms, Experimental; Pituitary Gland; Pituitary Neoplasms; Propylthiouracil; Thiouracil; Thyroid Gland; Thyroid Neoplasms