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2017 ; 36
(1
): 44
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Chrysin inhibited tumor glycolysis and induced apoptosis in hepatocellular
carcinoma by targeting hexokinase-2
#MMPMID28320429
Xu D
; Jin J
; Yu H
; Zhao Z
; Ma D
; Zhang C
; Jiang H
J Exp Clin Cancer Res
2017[Mar]; 36
(1
): 44
PMID28320429
show ga
BACKGROUND: Hexokinase-2(HK-2) plays dual roles in glucose metabolism and
mediation of cell apoptosis, making it an attractive target for cancer therapy.
Chrysin is a natural flavone found in plant extracts which are widely used as
herb medicine in China. In the present study, we investigated the antitumor
activity of chrysin against hepatocellular carcinoma (HCC) and the role of HK-2
played for chrysin to exert its function. METHODS: The expression of HK-2 in HCC
cell line and tumor tissue was examined by western blotting and
immunohistochemistry staining. The activities of chrysin against HCC cell
proliferation and tumor glycolysis were investigated. Chrysin-induced apoptosis
was analyzed by flow cytometry. The effect of chrysin on HK-2 expression and the
underlying mechanisms by which induced HCC cell apoptosis were studied. In HK-2
exogenous overexpression cell, the changes of chrysin-induced cell apoptosis and
glycolysis suppression were investigated. HCC cell xenograft model was used to
confirm the antitumor activity of chrysin in vivo and the effect on HK-2 was
tested in chrysin-treated tumor tissue. RESULTS: In contrast with normal cell
lines and tissue, HK-2 expression was substantially elevated in the majority of
tested HCC cell lines and tumor tissue. Owing to the decrease of HK-2 expression,
glucose uptake and lactate production in HCC cells were substantially inhibited
after exposure to chrysin. After chrysin treatment, HK-2 which combined with
VDAC-1 on mitochondria was significantly declined, resulting in the transfer of
Bax from cytoplasm to mitochondria and induction of cell apoptosis.
Chrysin-mediated cell apoptosis and glycolysis suppression were dramatically
impaired in HK-2 exogenous overexpression cells. Tumor growth in HCC xenograft
models was significantly restrained after chrysin treatment and significant
decrease of HK-2 expression was observed in chrysin-treated tumor tissue.
CONCLUSION: Through suppressing glycolysis and inducing apoptosis in HCC,
chrysin, or its derivative has a promising potential to be a novel therapeutic
for HCC management, especially for those patients with high HK-2 expression.