By blocking hexokinase-2 phosphorylation, limonin suppresses tumor glycolysis and induces cell apoptosis in hepatocellular carcinoma

OncoTargets and Therapy
Junliang YaoWensheng Zhao

Abstract

The purpose of present study was to investigate the effect of limonin on tumor glycolysis and the underlying mechanisms in hepatocellular carcinoma (HCC). Cell proliferation and colony formation assays were performed to evaluate the potency of limonin against HCC cells in vitro. The glucose consumption and lactate production after limonin treatment was determined. The effect of limonin on hexokinase-2 (HK-2) activity was assessed and the mitochondrial location of HK-2 was studied by immunoprecipitation. Cell apoptosis and protein expression were detected by flow cytometry and western blotting respectively. Protein overexpression by plasmid transfection was adopted to investigate the molecular mechanisms. HCC proliferation and colony formation were inhibited by limonin in vitro. With the suppression of HK-2 activity, the glycolytic level in HCC cells was substantially reduced, which was evidenced by the decrease of glucose consumption and lactate production. The phosphorylation of HK-2 was substantially inhibited by limonin, which resulted in the disassociation of HK-2 from mitochondria. Due to the reduction of HK-2 in mitochondria, increasing Bax were shifted to the mitochondria and gave rise to the release of cytochrome C, whi...Continue Reading

Citations

Oct 17, 2019·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Shunming FanLingying Yu
Mar 22, 2020·BMC Complementary Medicine and Therapies·Jae Ryul BaeKidong Kim
Feb 2, 2021·Journal of Cellular and Molecular Medicine·Chunmei GuoMing-Zhong Sun
Apr 13, 2021·Food Science & Nutrition·Yunyi ChenQingjun Chen
Dec 9, 2020·Journal of Medicinal Chemistry·Yulin Ren, A Douglas Kinghorn

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Methods Mentioned

BETA
Assay
immunoprecipitation
flow cytometry
FACS
transfection

Software Mentioned

Pro Plus
Image
Graphpad prism

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