Solid‐Phase Synthesis of a Combinatorial Methylated (±)‐Epigallocatechin Gallate Library and the Growth‐Inhibitory Effects of these Compounds on Melanoma B16 Cells

Tanaka, Hiroshi; Yamanouchi, Maasa; Miyoshi, Haruko; Hirotsu, Keisuke; Tachibana, Hirofumi; Takahashi, Takashi

doi:10.1002/asia.201000372

Cited by 34 publications

(12 citation statements)

References 48 publications

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“…For example, one of the methylation products, 7-OMe EGCG, was shown to have equal efficacy but increased bioavailability when compared to EGCG [26]. Given the aggressive nature of melanomas, effective therapies may most likely involve a combinational approach.…”

Section: Discussionmentioning

confidence: 99%

Green tea polyphenol epigallocatechin-3-gallate suppresses melanoma growth by inhibiting inflammasome and IL-1β secretion

Ellis

Liu

Luo

et al. 2011

Biochemical and Biophysical Research Communications

156

102

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Epigallocatechin-3-gallate (EGCG), the major polyphenolic component of green tea, has been demonstrated to possess anti-inflammatory, antioxidant, anti-mutagenic and anti-carcinogenic properties. The anti-melanoma effect of EGCG has been previously suggested, but no clear mechanism of action has been established. In this study, we demonstrated that EGCG inhibits melanoma cell growth at physiological doses (0.1–1 μM). In the search for mechanisms of EGCG-mediated melanoma cell suppression, we found that NF-κB was inhibited, and that reduced NF-κB activity was associated with decreased IL-1β secretion from melanoma cells. Since inflammasomes are involved in IL-1β secretion, we investigated whether IL-1β suppression was mediated by inflammasomes, and found that EGCG treatment led to downregulation of the inflammasome component, NLRP1, and reduced caspase-1 activation. Furthermore, silencing the expression of NLRP1 abolished EGCG-induced inhibition of tumor cell proliferation both in vitro and in vivo, suggesting a key role of inflammasomes in EGCG efficacy. This paper provides a novel mechanism for EGCG-induced melanoma inhibition: inflammasome downregulation → decreased IL-1β secretion → decreased NF-κB activities → decreased cell growth. In addition, it suggests inflammasomes and IL-1β could be potential targets for future melanoma therapeutics.

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Section: Discussionmentioning

confidence: 99%

Green tea polyphenol epigallocatechin-3-gallate suppresses melanoma growth by inhibiting inflammasome and IL-1β secretion

Ellis

Liu

Luo

et al. 2011

Biochemical and Biophysical Research Communications

156

102

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“…We found that the PDE5 inhibitor vardenafil sensitized MM cells to a methylated EGCG derivative that has been known to enhance pharmacokinetic characteristics compared with EGCG in plasma (43). Various types of EGCG derivatives can be produced by solidphase synthesis (44). Appropriate EGCG derivatives may improve the pharmacokinetic characteristics as activators of 67LR.…”

Section: Pde5 Is Overexpressed In Various Types Of Human Cancer and mentioning

confidence: 99%

67-kDa laminin receptor increases cGMP to induce cancer-selective apoptosis

Kumazoe

Sugihara²,

Tsukamoto³

et al. 2013

J. Clin. Invest.

Self Cite

111

215

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The 67-kDa laminin receptor (67LR) is a laminin-binding protein overexpressed in various types of cancer, including bile duct carcinoma, colorectal carcinoma, cervical cancer, and breast carcinoma. 67LR plays a vital role in growth and metastasis of tumor cells and resistance to chemotherapy. Here, we show that 67LR functions as a cancer-specific death receptor. In this cell death receptor pathway, cGMP initiated cancer-specific cell death by activating the PKCδ/acid sphingomyelinase (PKCδ/ASM) pathway. Furthermore, upregulation of cGMP was a rate-determining process of 67LR-dependent cell death induced by the green tea polyphenol (-)-epigallocatechin-3-O-gallate (EGCG), a natural ligand of 67LR. We found that phosphodiesterase 5 (PDE5), a negative regulator of cGMP, was abnormally expressed in multiple cancers and attenuated 67LR-mediated cell death. Vardenafil, a PDE5 inhibitor that is used to treat erectile dysfunction, significantly potentiated the EGCG-activated 67LR-dependent apoptosis without affecting normal cells and prolonged the survival time in a mouse xenograft model. These results suggest that PDE5 inhibitors could be used to elevate cGMP levels to induce 67LR-mediated, cancer-specific cell death.

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“…Takahashi and co-workers described the efficient solid-phase synthesis of EGCG (see Figure 1) and the combinatorial synthesis of protected methylated epicatechin derivatives 35 (2,3-disubstituted benzopyran derivatives) (Scheme 7) [61,62].…”

Section: Solid-phase Synthesis Of Substituted Benzopyran Compoundsmentioning

confidence: 99%

Solid-Phase Parallel Synthesis of Drug-Like Artificial 2H-Benzopyran Libraries

Lee

Gong

2012

Molecules

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This review covers the construction of drug-like 2H-benzopyrans and related libraries using solid-phase parallel synthesis. In this context, the preparation of substituted benzopyrans such as mono-, di-and trisubstituted benzopyran derivatives and additional ring-fused benzopyrans such as benzopyranoisoxazoles, benzopyranopyrazoles, six-membered ring-fused benzopyrans, and polycyclic benzopyrans are highlighted.

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Solid‐Phase Synthesis of a Combinatorial Methylated (±)‐Epigallocatechin Gallate Library and the Growth‐Inhibitory Effects of these Compounds on Melanoma B16 Cells

Cited by 34 publications

References 48 publications

Green tea polyphenol epigallocatechin-3-gallate suppresses melanoma growth by inhibiting inflammasome and IL-1β secretion

Green tea polyphenol epigallocatechin-3-gallate suppresses melanoma growth by inhibiting inflammasome and IL-1β secretion

67-kDa laminin receptor increases cGMP to induce cancer-selective apoptosis

Solid-Phase Parallel Synthesis of Drug-Like Artificial 2H-Benzopyran Libraries

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