methylthiouracil 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

Carminomycin chemotherapy of the patients with malignant tumors is often complicated with cardiopathy which is sometimes assymptomic and registered only electrocardiographycally. Chemotherapy on the background of reparative regeneration stimulators from the series of synthetic pyrrimidine derivatives, such as methyluracyl for oral use and a soluble salt of methyluracyl for parenteral administration significantly decreased the rate of the cardiotoxic complications and promoted a decrease in their level. The use of methyluracyl and its soluble salt did not decrease the therapeutic effect of carminomycin. Methyluracyl and its soluble salt may be recommended for prophylaxis of cardiotoxic complications in chemotherapy of malignant tumors with carminomycin.

Topics: Adult; Aged; Antibiotics, Antineoplastic; Carubicin; Clinical Trials as Topic; Drug Evaluation; Drug Interactions; Drug Therapy, Combination; Heart; Humans; Methylthiouracil; Middle Aged; Neoplasm Metastasis; Neoplasms

Topics: Age Factors; Animals; Cell Differentiation; Cell Nucleus; Cell Transformation, Neoplastic; Embryo, Mammalian; Endoplasmic Reticulum; Female; Histological Techniques; Inclusion Bodies; Lysosomes; Methylthiouracil; Mice; Microscopy; Microscopy, Electron; Mitochondria; Neoplasms; Neoplasms, Experimental; Organoids; Ribosomes; Staining and Labeling; Thyroid Gland; Thyroid Neoplasms

Topics: Aged; Female; Humans; Inflammation; Male; Methylthiouracil; Neoplasms; Skin; Skin Window Technique; Surgical Wound Dehiscence; Triiodothyronine; Wound Healing

Topics: Alloxan; Carbon Tetrachloride Poisoning; Chemical and Drug Induced Liver Injury; Cortisone; Estradiol; Hepatitis; Histocytochemistry; Hormones; Humans; Male; Methylthiouracil; Neoplasms; Neoplasms, Experimental; Physiology; Prolactin; Prostate; Prostatic Neoplasms; Rats; Research; Testosterone; Thymidine; Thyroid Hormones; Zinc Isotopes

Topics: Adenoma; Carcinogens; Methylthiouracil; Neoplasms; Neoplasms, Experimental; Pharmacology; Pituitary Neoplasms; Rats; Research; Thyroid Gland; Thyroid Neoplasms; Transplantation

Topics: Adrenal Gland Neoplasms; Adrenalectomy; Breast Neoplasms; Castration; Cortisone; Electrons; Endocrine Glands; Humans; Male; Methylthiouracil; Microscopy; Microscopy, Electron; Neoplasms; Neoplasms, Experimental; Ovarian Neoplasms; Pathology; Pituitary Gland; Pituitary Neoplasms; Prostatic Neoplasms; Rats; Research; Testicular Neoplasms; Thyroid Neoplasms; Thyroidectomy

Topics: Carcinogenesis; Methylthiouracil; Neoplasms; Neoplasms, Experimental; Rats; Research; Thyroid Neoplasms; Triazoles

Topics: Adenoma; Goiter; Histology; Humans; Iodine; Methylthiouracil; Neoplasm Metastasis; Neoplasms; Pathology; Thyroid Neoplasms

Topics: Adenocarcinoma; Carcinogens; Kidney Diseases, Cystic; Kidney Neoplasms; Methylthiouracil; Neoplasms; Neoplasms, Experimental; Pathology; Rats; Research

Topics: Animals; Fluorenes; Methylthiouracil; Neoplasms; Neoplasms, Experimental; Thiouracil; Thyroid Gland; Thyroid Neoplasms

Topics: Animals; Methylthiouracil; Neoplasms; Neoplasms, Experimental; Rats; Thiouracil; Thyroid Gland; Thyroid Neoplasms

Topics: Hyperthyroidism; Methylthiouracil; Neoplasms; Thiazoles; Thiouracil

Topics: Animals; Iodine; Iodine Radioisotopes; Methylthiouracil; Neoplasms; Neoplasms, Experimental; Thiouracil; Thyroid Gland; Thyroid Neoplasms

Topics: 2-Acetylaminofluorene; Adenoma; Iodine; Iodine Compounds; Lymphoma, Non-Hodgkin; Methylthiouracil; Neoplasms; Sarcoma; Thyroid Gland

Topics: Acetamides; Animals; Methylthiouracil; Neoplasms; Rats; Thiouracil; Thyroid Gland; Thyroxine

Topics: Adrenal Gland Neoplasms; Adrenal Glands; Blood Pressure; Humans; Hypertension; Methylthiouracil; Neoplasms; Pheochromocytoma; Thiouracil