Mechanistic Aspects of Green Tea as a Cancer Preventive: Effect of Components on Human Stomach Cancer Cell Lines

Okabe, Sachiko; Ochiai, Yumiko; Aida, Miwa; Park, Keunchil; Kim, Seong‐Jin; Nomura, Taro; Suganuma, Masami; Fujiki, Hirota

doi:10.1111/j.1349-7006.1999.tb00808.x

Cited by 127 publications

(81 citation statements)

References 20 publications

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“…EGCG inhibited TPA-induced transcriptional activity of NF-kB and its DNA binding in JB6 mouse epidermal cell lines, which could be correlated with the blockage of phosphorylation of IkBa at Ser32 (Nomura et al, 2000). EGCG also inhibited TNF-a gene expression and okadaic acid-induced DNA binding of NF-kB and AP-1 transcriptional factors in KATO III cells (Okabe et al, 1999) and in RAW 264.7 cell lines stimulated with lipopolysaccharides (Yang et al, 1998).…”

Section: Discussionmentioning

confidence: 87%

Inhibition of ultraviolet B-mediated activation of nuclear factor κB in normal human epidermal keratinocytes by green tea Constituent (-)-epigallocatechin-3-gallate

et al. 2003

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Epigallocatechin-3-gallate (EGCG), the major constituent of green tea, possesses significant anti-inflammatory and cancer chemopreventive properties. Studies have shown the photochemopreventive effects of green tea and EGCG in cell culture, animal models, and human skin. The molecular mechanism(s) of photochemopreventive effects of EGCG are incompletely understood. We recently showed that EGCG treatment of the normal human epidermal keratinocytes (NHEK) inhibits ultraviolet (UV)B-mediated activation of the mitogen-activated protein kinase (MAPK) pathway. In this study, we evaluated the effect of EGCG on UVB-mediated modulation of the nuclear factor kappa B (NF-jB) pathway, which is known to play a critical role in a variety of physiological functions and is involved in inflammation and development of cancer. Immunoblot analysis demonstrated that the treatment of NHEK with EGCG (10-40 lm) for 24 h resulted in a significant inhibition of UVB (40 mJ/cm 2 )-mediated degradation and phosphorylation of IjBa and activation of IKKa, in a dose-dependent manner. UVB-mediated degradation and phosphorylation of IjBa and activation of IKKa was also observed in a time-dependent protocol (15 and 30 min, 1, 2, 3, 6, 12 h post-UVB exposure). Employing immunoblot analysis, enzyme-linked immunosorbent assay, and gel shift assay, we demonstrate that EGCG treatment of the cells resulted in a significant dose-and time-dependent inhibition of UVB-mediated activation and nuclear translocation of a NF-jB/p65. Our data suggest that EGCG protects against the adverse effects of UV radiation via modulations in NF-jB pathway, and provide a molecular basis for the photochemopreventive effect of EGCG.

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Section: Discussionmentioning

confidence: 87%

Inhibition of ultraviolet B-mediated activation of nuclear factor κB in normal human epidermal keratinocytes by green tea Constituent (-)-epigallocatechin-3-gallate

et al. 2003

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“…EGCG significantly suppressed cancer-invasive ability in oral cancer cell lines by decreasing the number of invasive foci and depth of invasion as strong as classical DNMT inhibitor, 5-aza-dC. Oral administration of green tea has been reported to inhibit tumour genesis in different organs and multiple mechanisms may be involved (Jung and Ellis, 2000;Khan et al, 2006;Chiang et al, 2006;Okabe et al, 1999). Importantly, these effects of EGCG have been shown to be selective for cancer cells, as normal cells were not affected by this treatment (Khan et al, 2006).…”

Section: Discussionmentioning

confidence: 92%

“…However, our data demonstrate that OSCC cell lines-derived MMP-2 and MMP-9 were inhibited at 50 mM of EGCG treatment. Previous studies showed that restored expression of RECK in malignant cells resulted in suppression of invasive activity with concomitant decrease in the secretion of MMPs (Takahashi et al, 1998;Okabe et al, 1999;Liu et al, 2003;Noda et al, 2003). Treatment with EGCG, HSC3 and HSC4 cells cultured on top of collagen gels produced widespread but shallow foci of invasion whereas control cells (EGCG-free medium) invaded and generated large and deep pits extending well in the collagen matrix.…”

Section: Discussionmentioning

confidence: 99%

Effects of green tea polyphenol on methylation status of RECK gene and cancer cell invasion in oral squamous cell carcinoma cells

et al. 2008

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RECK is a novel tumour suppressor gene that negatively regulates matrix metalloproteinases (MMPs) and inhibits tumour invasion, angiogenesis and metastasis. In the present study, we investigated the effects of epigallocatechin-3-gallate (EGCG), a major polyphenol in green tea, on the methylation status of the RECK gene and cancer invasion in oral squamous cell carcinoma cell lines. Our results showed that treatment of oral cancer cells with EGCG partially reversed the hypermethylation status of the RECK gene and significantly enhanced the expression level of RECK mRNA. Inhibition of MMP-2 and MMP-9 levels was also observed in these cells after treatment with EGCG. Interestingly, EGCG significantly suppressed cancer cell-invasive ability by decreasing the number of invasive foci (Po0.0001) as well as invasion depth (Po0.005) in three-dimensional collagen invasion model. Although further investigation is required to assess the extent of contribution of RECK on MMPs to the suppression of invasive behaviour, these results support the conclusion that EGCG plays a key role in suppressing cell invasion through multiple mechanisms, possibly by demethylation effect on MMP inhibitors such as RECK.

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“…6) However, in a practical sense, it is quantitatively easier to measure inhibition of TNF-a release from cells treated with a tumor promoter such as okadaic acid than inhibition of NFkB activation using a gel mobility shift assay. 7) Based on the study of green tea as cancer preventive agent in the United States 8) and as cancer preventive beverage in Japan, 9) we decided to take a closer look at Japanese herbal medicine for other likely cancer preventives. One classical Japanese herb, Geranium thunbergii SIEB.…”

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confidence: 99%

New TNF-.ALPHA. Releasing Inhibitors, Geraniin and Corilagin, in Leaves of Acer nikoense, Megusurino-ki.

Okabe

Suganuma

Imayoshi

et al. 2001

Biological & Pharmaceutical Bulletin

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We have recently reported that inhibition of tumor necrosis factor-a (TNF-a) release is a useful method for screening of cancer preventive agents, 1) because TNF-a and other inflammatory cytokines stimulate tumor promotion and progression of initiated cells as well as premalignant cells. 2,3) Since TNFa and interleukin-1 (IL-1), as endogenous tumor promoters, activate nuclear factor kB (NF-kB), 4,5) inhibitors of NF-kB activation are also assumed to be cancer preventive agents. 6) However, in a practical sense, it is quantitatively easier to measure inhibition of TNF-a release from cells treated with a tumor promoter such as okadaic acid than inhibition of NFkB activation using a gel mobility shift assay. 7) Based on the study of green tea as cancer preventive agent in the United States 8) and as cancer preventive beverage in Japan, 9) we decided to take a closer look at Japanese herbal medicine for other likely cancer preventives. One classical Japanese herb, Geranium thunbergii SIEB. et ZUCC. (Gennoshoko in Japanese), is used as an antidiarrhetic 10) ; it contains geraniin, which has been intensively studied as a representative tannin. 11) And the bark of Acer nikoense MAXIM (Megusurino-ki in Japanese), which contains diarylheptanoids, is sold as a folk medicine for eye and liver diseases in Japan. 12) The Forestry Experiment Station of Saitama Prefecture succeeded in culturing young plants of A. nikoense collaborated with us on the scientific utilization of the plant. We received four water extracts-leaves, bark, small branches, and timber-from the Station and subjected them to inhibition of TNF-a release assay using BALB/3T3 cells treated with okadaic acid 13) : The leaves showed the strongest activity among the four extracts. Each extract was subjected to highperformance liquid chromatography (HPLC) with CAP-CELL PAK C18, and geraniin and corilagin were identified in the active leaf extract (Fig. 1).In The success of green tea as a cancer preventive is based on evidence that green tea contains tannins and antioxidants, does not show toxicity in humans and has long traditional use in Asia. In the light of this, herbal medicines are now also attracting attention as potential sources of cancer preventive agents. Using the inhibition of TNF-a a release assay, we studied Acer nikoense (Megusurino-ki in Japanese), one of the herbal medicines. The inhibitory activity of TNF-a a release was found in the leaf extract rather than the bark extract, and the main active constituents were identified as geraniin and corilagin, which are present in another Japanese traditional herb, Geranium thunbergii (Genno-shoko). The IC 50 values of TNF-a a release inhibition were 43 m mM for geraniin and 76 m mM for corilagin, whereas that for (؊)-epigallocatechin gallate (EGCG) was 26 m mM. Treatment with geraniin prior to application of okadaic acid, a tumor promoter on mouse skin initiated with 7,12-dimethylbenz(a)anthracene, reduced the percentage of tumor-bearing mice from 80.0 to 40.0% and the average numbers of tumor per mouse ...

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Mechanistic Aspects of Green Tea as a Cancer Preventive: Effect of Components on Human Stomach Cancer Cell Lines

Abstract: It is now well accepted that (−

Cited by 127 publications

References 20 publications

Inhibition of ultraviolet B-mediated activation of nuclear factor κB in normal human epidermal keratinocytes by green tea Constituent (-)-epigallocatechin-3-gallate

Inhibition of ultraviolet B-mediated activation of nuclear factor κB in normal human epidermal keratinocytes by green tea Constituent (-)-epigallocatechin-3-gallate

Effects of green tea polyphenol on methylation status of RECK gene and cancer cell invasion in oral squamous cell carcinoma cells

New TNF-.ALPHA. Releasing Inhibitors, Geraniin and Corilagin, in Leaves of Acer nikoense, Megusurino-ki.

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