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Insights into Glycogen Metabolic Inhibition‐Induced Death of Hepatocellular Carcinoma
Author(s) -
Barot Shrikant,
AboAli Ehab M.,
Palaguachi Christian,
Dukhande Vikas V.
Publication year - 2018
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.2018.32.1_supplement.811.15
Subject(s) - glycogen , cancer cell , programmed cell death , autophagy , biology , glycolysis , carcinogenesis , cancer research , metastasis , glycogen synthase , cancer , apoptosis , reprogramming , anaerobic glycolysis , cell , microbiology and biotechnology , biochemistry , metabolism , genetics
Metabolic reprogramming is one of the prominent features of cancer. Cancer metabolic reprogramming offers various advantages for proliferation, invasion, metastasis, and chemoresistance. Cancer cells are highly glycolytic, a phenomenon termed as Warburg effect or aerobic glycolysis , with concomitant increase in the amount of glucose entering the cells. Glycogen is a storage form of glucose and the levels of glycogen have been found to change with biological processes in these reprogrammed cells. Glycogen Phosphorylase (Gp) is a rate‐limiting enzyme that catabolizes glycogen to glucose. The contribution of glycogen metabolism to carcinogenesis, cancer cell growth, metastasis, and chemoresistance is poorly understood. Thus, we aimed to mechanistically study the processes involved in GP inhibition‐induced hepatocellular carcinoma cell death. We pharmacologically inhibited glycogen catabolism in HepG2 cells and found that there was a decrease in cell viability in a dose‐dependent manner. Next, we measured the major markers for apoptosis, necrosis, and autophagy. Our results indicate that GP‐inhibition induces cancer cell death through apoptosis process. In addition, GP inhibition potentiates the effects of known anti‐cancer drugs. Our ongoing studies will identify the key molecular components involved in apoptotic and autophagic processes in glycogen inhibition‐induced cell death. Our study provides insights into cancer cell metabolism and identifies GP‐inhibition as a potential cancer pharmacology target. Support or Funding Information Supported by startup funds to Dr. Dukhande from St. John's University, College of Pharmacy and Health Sciences. This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .