Department of Pharmaceutical Sciences, College of Pharmacy and Health Sciences, St. John's University, Queens, NY, USA. Electronic address:
Published: August 2019
AI Article Synopsis
Article Abstract
Hepatocellular carcinoma (HCC) is one of the leading cancers in the world in incidence and mortality. Current pharmacotherapy of HCC is limited in the number and efficacy of anticancer agents. Metabolic reprogramming is a prominent feature of many cancers and has rekindled interest in targeting metabolic proteins for cancer therapy. Glycogen is a storage form of glucose, and the levels of glycogen have been found to correlate with biological processes in reprogrammed cancer cells. However, the contribution of glycogen metabolism to carcinogenesis, cancer cell growth, metastasis, and chemoresistance is poorly understood. Thus, we studied the processes involved in the inhibition of glycogen metabolism in HCC cells. Pharmacological inhibition of glycogen phosphorylase (GP), a rate-limiting enzyme in glycogen catabolism, by CP-91149 led to a decrease in HCC cell viability. GP inhibition induced cancer cell death through the intrinsic apoptotic pathway. Mitochondrial dysfunction and autophagic adaptations accompanied this apoptosis process whereas endoplasmic reticulum stress, necrosis, and necroptosis were not major components of the cell death. In addition, GP inhibition potentiated the effects of multikinase inhibitors sorafenib and regorafenib, which are key drugs in advanced-stage HCC therapy. Our study provides mechanistic insights into cell death by perturbation of glycogen metabolism and identifies GP inhibition as a potential HCC pharmacotherapy target.
Section of Infection and Immunity, Herman Ostrow School of Dentistry, Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, CA 90089, USA. Electronic address:
Metabolism is typically contextualized in conjunction with proliferation and growth. The roles of metabolic enzymes beyond metabolism-such as in innate immune responses-are underexplored. Using a focused short hairpin RNA (shRNA)-mediated screen, we identified CTP synthetase 1 (CTPS1), a rate-limiting enzyme of pyrimidine synthesis, as a negative regulator of interferon induction.
Background: Fibrosis is key in the development and progression of diabetic kidney disease (DKD). Baicalin (BA), wogonin (WGN), and wogonoside (WGS) have renoprotective effects. The mechanism of alleviation of DKD progression, by improving renal fibrosis, is unclear.
Department of Cardiology, Laboratory of Heart Center, Zhujiang Hospital, Southern Medical University, No 253, Middle Gongye Avenue, 510282, Guangzhou, Guangdong, People's Republic of China.
Doxorubicin-induced cardiotoxicity (DIC) poses a threat to the health and prognosis of cancer patients. It is important to find a safe and effective method for the prevention and treatment of DIC. eEF2K, which is a highly conserved α-kinase, is thought to be a therapeutic target for several human diseases.
Background: While NDUFAF6 is implicated in breast cancer, its specific role remains unclear.
Methods: The expression levels and prognostic significance of NDUFAF6 in breast cancer were assessed using The Cancer Genome Atlas, Gene Expression Omnibus, Kaplan-Meier plotter and cBio-Portal databases. We knocked down NDUFAF6 in breast cancer cells using small interfering RNA and investigated its effects on cell proliferation and migration ability.
Department of Respiratory and Critical Care Medicine, Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing 210028, China. Electronic address:
Background: Astragaloside II (AST II) is one of the principal bioactive components of Astragalus mongholicus Bunge, exhibiting multiple pharmacological properties. However, the therapeutic efficacy of AST II in Chronic Obstructive Pulmonary Disease (COPD) remains to be fully elucidated. The study explored the effects and mechanisms of AST II in a COPD model induced by exposure to cigarette smoke (CS) and lipopolysaccharide (LPS) in mice.
