Metabolite modulation of HeLa cell response to ENOX2 inhibitors EGCG and phenoxodiol

Wu, Lei; Luca, Thomas De; Watanabe, Takahiro; Morré, Dorothy M.; Morré, D. James

doi:10.1016/j.bbagen.2011.04.011

Cited by 8 publications

(3 citation statements)

References 35 publications

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“…Ceramide plays a role as second messenger in the signal transduction, inducing lipid raft clustering and the stabilization of DISC complex, amplification of Fas/FasL signalling, finally leading to apoptosis [155,158,159]. A similar mechanism has been hypothesized in the case of cervical, prostate and colon cancer, where EGCG administration induces cell apoptosis through aSMase activation and ceramide increase [160,161,162].…”

Section: 67-kda Laminin Receptor Signalling Pathwaysmentioning

confidence: 98%

Molecular Targets of Epigallocatechin—Gallate (EGCG): A Special Focus on Signal Transduction and Cancer

et al. 2018

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Green tea is a beverage that is widely consumed worldwide and is believed to exert effects on different diseases, including cancer. The major components of green tea are catechins, a family of polyphenols. Among them, epigallocatechin-gallate (EGCG) is the most abundant and biologically active. EGCG is widely studied for its anti-cancer properties. However, the cellular and molecular mechanisms explaining its action have not been completely understood, yet. EGCG is effective in vivo at micromolar concentrations, suggesting that its action is mediated by interaction with specific targets that are involved in the regulation of crucial steps of cell proliferation, survival, and metastatic spread. Recently, several proteins have been identified as EGCG direct interactors. Among them, the trans-membrane receptor 67LR has been identified as a high affinity EGCG receptor. 67LR is a master regulator of many pathways affecting cell proliferation or apoptosis, also regulating cancer stem cells (CSCs) activity. EGCG was also found to be interacting directly with Pin1, TGFR-II, and metalloproteinases (MMPs) (mainly MMP2 and MMP9), which respectively regulate EGCG-dependent inhibition of NF-kB, epithelial-mesenchimal transaction (EMT) and cellular invasion. EGCG interacts with DNA methyltransferases (DNMTs) and histone deacetylases (HDACs), which modulates epigenetic changes. The bulk of this novel knowledge provides information about the mechanisms of action of EGCG and may explain its onco-suppressive function. The identification of crucial signalling pathways that are related to cancer onset and progression whose master regulators interacts with EGCG may disclose intriguing pharmacological targets, and eventually lead to novel combined treatments in which EGCG acts synergistically with known drugs.

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Section: 67-kda Laminin Receptor Signalling Pathwaysmentioning

confidence: 98%

Molecular Targets of Epigallocatechin—Gallate (EGCG): A Special Focus on Signal Transduction and Cancer

et al. 2018

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“…Another mechanism of Cer-mediated apoptosis proposed by Wu et al [ 62 ] involves ENOX2 (tNOX) inhibition by EGCG. Inhibition of the ENOX family commonly results in an accumulation of cytosolic NADH at the inner leaflet of the plasma membrane.…”

Section: Focus On Cancer: Dietary Polyphenols and Sphingolipidsmentioning

confidence: 99%

Cancer Prevention and Therapy with Polyphenols: Sphingolipid-Mediated Mechanisms

Dei

Ghidoni

2018

Nutrients

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Polyphenols, chemically characterized by a polyhydroxylated phenolic structure, are well known for their widespread pharmacological properties: anti-inflammatory, antibiotic, antiseptic, antitumor, antiallergic, cardioprotective and others. Their distribution in food products is also extensive especially in plant foods such as vegetables, cereals, legumes, fruits, nuts and certain beverages. The latest scientific literature outlines a resilient interconnection between cancer modulation and dietary polyphenols by sphingolipid-mediated mechanisms, usually correlated with a modification of their metabolism. We aim to extensively survey this relationship to show how it could be advantageous in cancer treatment or prevention by nutrients. From this analysis it emerges that a combination of classical chemotherapy with nutrients and especially with polyphenols dietary sources may improve efficacy and decreases negative side effects of the antineoplastic drug. In this multifaceted scenario, sphingolipids play a pivotal role as bioactive molecules, emerging as the mediators of cell proliferation in cancer and modulator of chemotherapeutics.

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“…32 Phenoxodiol presented several promising and encouraging results, as the ability to increase the effectiveness of docetaxel in drug resistant ovarian carcinoma cells by at least 100 times, 33 besides having an inhibitory effect against Topoisomerase 2 in the same range of etoposide, but stronger than genistein. 34 Despite this, phenoxodiol failed in clinical trials for recurrent ovarian carcinoma aer the "fast track" status for clinical use provided by FDA, 9 the molecule (or its derivatives) still arouses great scientic [35][36][37][38] and economical interest, especially from the pharmaceutical industry. 39 Flavopiridol is another semisynthetic avonoid with potential anticancer properties.…”

Section: Flavonoids and Anticancer Therapymentioning

confidence: 99%

Flavonoids from Achyrocline satureioides: promising biomolecules for anticancer therapy

2014

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Cancer is the major public health problem worldwide; consequently, the search for new chemotherapeutic drugs is constant. Most of these agents are derived from natural sources, which are the major consistent basis for the search for modern anticancer medicines. In this context, numerous studies indicate flavonoids as a potential new class of secondary metabolites for anticancer therapy. In this review, special attention was addressed to flavonoids present in Achyrocline satureioides, a widely used medicinal plant with several and a well established range of biological properties. Two of these flavonoids are extensively studied for anticancer therapy, quercetin and luteolin, followed by 3-Omethylquercetin. Achyrobichalcone, recently isolated from A. satureioides by our group, can also represent a promising chemotherapeutic biomolecule due to its similarity with other cytotoxic bichalcones to cancer cell lines. The anticancer properties of these flavonoids, specially quercetin and luteolin, type of cell death, mechanisms and molecular targets involved were described. In general, these effects were observed due to the inhibition of cell proliferation, cell cycle arrest, apoptosis, inhibition of angiogenesis, prevention of migration/metastasis and overcoming multidrug resistance, alone or in combination with commonly used chemotherapeutic drugs. All these successful findings in preclinical studies suggest that these flavonoids are promising biomolecules for the development of new anticancer drugs in the future.

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Metabolite modulation of HeLa cell response to ENOX2 inhibitors EGCG and phenoxodiol

Cited by 8 publications

References 35 publications

Molecular Targets of Epigallocatechin—Gallate (EGCG): A Special Focus on Signal Transduction and Cancer

Molecular Targets of Epigallocatechin—Gallate (EGCG): A Special Focus on Signal Transduction and Cancer

Cancer Prevention and Therapy with Polyphenols: Sphingolipid-Mediated Mechanisms

Flavonoids from Achyrocline satureioides: promising biomolecules for anticancer therapy

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