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Anti-cancer properties of glucosamine-hydrochloride in YD-8 human oral cancer cells: Induction of the caspase-dependent apoptosis and down-regulation of HIF-1α

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Affiliated Author(s)
남기영박종욱송대규배재훈장병철하정숙
Alternative Author(s)
Nam, Ki YoungPark, Jong WookSong, Dae KyuBae, Jae HoonJang, Byeong ChurlHa, Jung Sook
Journal Title
Toxicol In Vitro
ISSN
0887-2333
Issued Date
2012
Keyword
YD-8 cellsGlucosamine-HClCaspasesER stressHIF-1aMcl-1
Abstract
Evidence suggests anti-tumor activities of glucosamine-hydrochloride (GS-HCl). In the present study, we
investigated anti-proliferative, growth suppressive and/or pro-apoptotic effects of GS-HCl on YD-8
human oral squamous cell carcinoma (OSCC) cells. Fundamentally, treatment with GS-HCl strongly inhib-
ited proliferation and induced apoptosis in YD-8 cells, as determined by MTS and DNA fragmentation
analyses. Of further note, as measured by Western analyses, GS-HCl treatment led to activation of cas-
pase-3, cytosolic accumulation of cytochrome c, down-regulation of Mcl-1 and HIF-1a, up-regulation
of GRP78, an indicator of ER stress, and generation of ROS in YD-8 cells. Importantly, results of pharma-
cological inhibition studies showed that treatment with z-VAD-fmk, a pan-caspase inhibitor, but not with
vitamin E, an anti-oxidant strongly blocked the GS-HCl-induced apoptosis in YD-8 cells. Analyses of addi-
tional cell culture works further revealed that GS-HCl had a strong growth suppressive effect on not only
YD-8 but also YD-10B and YD-38, two other human OSCC cell lines. These findings collectively demon-
strate that GS-HCl has anti-proliferative, anti-survival, and pro-apoptotic effects on YD-8 cells and the
effects appear to be mediated via mechanisms associated with the mitochondrial-dependent activation
of caspases, down-regulation of Mcl-1, and induction of ER stress. Considering HIF-1a as a tumor angio-
genic transcription factor, the ability of GS-HCl to down-regulate HIF-1a in YD-8 cells may further sup-
port its anti-cancer property. It is thus suggested that GS-HCl may be used as a potential anti-cancer drug
against human OSCC. Keywords:
YD-8 cells
Glucosamine-HCl
Caspases
ER stress
HIF-1a
Mcl-1
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