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Inhibitory effect of gingerol on the proliferation and invasion of hepatoma cells in culture.

ABSTRACT: Effect of [6]-gingerol, a major pungent component in ginger, on the proliferation of a rat ascites hepatoma AH109A cells was investigated by measuring [(3)H]thymidine incorporation into acid-insoluble fraction of the cultured cells and that on the invasion by co-culturing the hepatoma cells with rat mesentery-derived mesothelial cells. [6]-Gingerol inhibited both the proliferation and invasion of hepatoma cells in a dose-dependent manner at concentrations of 6.25-200 muM (proliferation) and 50-200 muM (invasion). [6]-Gingerol accumulated cells in S phase and elongated doubling time of hepatoma cells, and increased the rate of apoptosis. Hepatoma cells previously cultured with hypoxanthine (HX) and xanthine oxidase (XO) or with hydrogen peroxide showed increased invasive activities. [6]-Gingerol suppressed the reactive oxygen species-potentiated invasive capacity by simultaneously treating AH109A cells with [6]-gingerol, HX and XO or with [6]-gingerol and hydrogen peroxide. Furthermore, [6]-gingerol reduced the intracellular peroxide levels in AH109A cells. These results suggest that the suppression of hepatoma cell proliferation by [6]-gingerol may be due to cell cycle arrest and apoptosis induction. They also suggest that the anti-oxidative property of [6]-gingerol may be involved in its anti-invasive activity of hepatoma cells.

SUBMITTER: Yagihashi S

PROVIDER: S-EPMC2553670 | biostudies-other | 2008 Jun

REPOSITORIES: biostudies-other

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Project description:Background: Zinc finger and scan domain containing 18 (ZSCAN18) belongs to zinc finger transcription factor superfamily, which consists of the hundreds of members that play critical roles in all steps of tumorigenesis. Although hypermethylation of ZSCAN18 promoter and its consequent deficiency in a variety of malignancies has been reported recently, its functions and mechanisms in the initiation and progression of gastric cancer (GC) are not clear. This study aims to investigate the roles of ZSCAN18 in gastric carcinogenesis. Methods: Methylation of ZSCAN18 promoter in GC cell lines were analyzed via MassARRAY and treatment of 5-Aza-2'-deoxycytidine. Bioinformatics analysis, qRT-PCR, western blot, immunohistochemistry, CCK-8, colony formation, and in vivo xenograft tumor model were used to examine the expression and function of ZSCAN18. Survival analysis was performed to determine the correlation between ZSCAN18 expression and prognosis of patients with GC. Genes modulated by ZSCAN18 in NCI-N87 cells were identified through RNA next generation sequence screening and further verified by qRT-PCR in AGS and NCI-N87 cells. Results: ZSCAN18 expression was markedly reduced in GC tissues as compared with that in adjacent normal tissues due to hypermethylation in GC. Likewise, ZSCAN18 expression was also significantly reduced in a panel of GC cell lines as the result of densely methylated ZSCAN18 promoter. Forced expression of ZSCAN18 inhibited proliferation in AGS and NCI-N87 cells in vitro. Additionally, ZSCAN18 impaired growth of NCI-N87 cells in immunodeficient mice. Survival analysis showed that ZSCAN18 expression was positively associated with favorable outcome in patients with GC. RNA next generation sequence screening showed three representative genes (FGF20, CEACAM5 and TP53INP2) involved in downstream signaling pathways modulated by ZSCAN18. Conclusions: Collectively, this study unveils the anti-cancer role of ZSCAN18 in GC, providing a promising diagnostic and therapeutic target.

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Inhibitory effect of gingerol on the proliferation and invasion of hepatoma cells in culture.

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