Inhibitory effects of polyphenols isolated from Rhus verniciflua on Aldo-keto reductase family 1 B10

Song, Dae Geun; Lee, Joo Young; Lee, Eun Ha; Jung, Sang Hoon; Nho, Chu Won; Hyun, Kwang; Koo, Song Yi; Pan, Cheol Ho

doi:10.5483/bmbrep.2010.43.4.268

Cited by 16 publications

(16 citation statements)

References 24 publications

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“…Cys299 is located close to the active site and modulates the interaction Given the important implications of AKR1B10 in tumor development and cancer chemoresistance, the search for inhibitors of this enzyme is a thriving area of research. Several compounds have been found to display AKR1B10 inhibitory properties in vitro, including some nonsteroidal anti-inflammatory drugs (41), butein (42), and curcumin derivatives (43). Our results suggest that PGA-type cyPG may constitute a novel class of AKR inhibitors.…”

Section: Discussionmentioning

confidence: 70%

Identification of Aldo-Keto Reductase AKR1B10 as a Selective Target for Modification and Inhibition by Prostaglandin A1: Implications for Antitumoral Activity

et al. 2011

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Cyclopentenone prostaglandins (cyPG) are reactive eicosanoids that may display anti-inflammatory and antiproliferative actions, possibly offering therapeutic potential. Here we report the identification of members of the aldo-keto reductase (AKR) family as selective targets of the cyPG prostaglandin A 1 (PGA 1 ). AKR enzymes metabolize aldehydes and drugs containing carbonyl groups and are involved in inflammation and tumorigenesis. Thus, these enzymes represent a class of targets to develop small molecule inhibitors with therapeutic activity. Molecular modeling studies pointed to the covalent binding of PGA 1 to Cys299, close to the active site of AKR, with His111 and Tyr49, which are highly conserved in the AKR family, playing a role in PGA 1 orientation. Among AKR enzymes, AKR1B10 is considered as a tumor marker and contributes to tumor development and chemoresistance. We validated the direct modification of AKR1B10 by biotinylated PGA 1 (PGA 1 -B) in cells, and confirmed that mutation of Cys299 abolishes PGA 1 -B incorporation, whereas substitution of His111 or Tyr49 reduced the interaction. Modification of AKR1B10 by PGA 1 correlated with loss of enzymatic activity and both effects were increased by depletion of cellular glutathione. Moreover, in lung cancer cells PGA 1 reduced tumorigenic potential and increased accumulation of the AKR substrate doxorubicin, potentiating cell-cycle arrest induced by this chemotherapeutic agent. Our findings define PGA 1 as a new AKR inhibitor and they offer a framework to develop compounds that could counteract cancer chemoresistance. Cancer Res; 71(12); 4161-71. Ó2011 AACR.

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Section: Discussionmentioning

confidence: 70%

Identification of Aldo-Keto Reductase AKR1B10 as a Selective Target for Modification and Inhibition by Prostaglandin A1: Implications for Antitumoral Activity

et al. 2011

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“…Compounds isolated from R. verniciflua showed potent inhibitory effects on AKR1B1 and AKR1B10 [106,107]. Song et al [28] reported that butein (19) extracted from R. verniciflua was a potent uncompetitive inhibitor for AKR1B10 and its inhibition pattern was the same as that found against AKR1B1 [106], although its potency against AKR1B1 was slightly higher. Numerous former studies have indicated that human bladder carcinoma and hepatoma could also be suppressed by butein through various mechanisms [108,109].…”

Section: Natural-based Derivativesmentioning

confidence: 82%

“…The above substances were also reported to present antitumor properties [99][100][101][102], and the inhibition effect on AKR1B10 might be one of mechanisms on their anticancer activities. Other plant polyphenols, such as butein (WO2014081124) [103] isolated from Rhus verniciflua, a medicinal plant, and dicaffeoyl quinic acid (CN104710312) [104] were also reported to can inhibit AKR1B10 [28,105]. Compounds isolated from R. verniciflua showed potent inhibitory effects on AKR1B1 and AKR1B10 [106,107].…”

Section: Natural-based Derivativesmentioning

confidence: 99%

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Aldo-Keto Reductase Family 1 Member B10 Inhibitors: Potential Drugs for Cancer Treatment

Li¹,

He²,

Luo³

et al. 2016

PRA

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Cytosolic NADPH-dependent reductase AKR1B10 is a member of the aldo-keto reductase (AKR) superfamily. This enzyme is normally expressed in the gastrointestinal tract. However, it is overexpressed in many solid tumors, such as hepatocarcinoma, lung cancer and breast cancer. AKR1B10 may play a role in the formation and development of carcinomas through multiple mechanisms including detoxification of cytotoxic carbonyls, modulation of retinoic acid level, and regulation of cellular fatty acid synthesis and lipid metabolism. Studies have suggested that AKR1B10 may be a useful biomarker for cancer diagnosis and a potential target for cancer treatment. Over the last decade, a number of AKR1B10 inhibitors including aldose reductase inhibitors (ARIs), endogenous substances, natural-based derivatives and synthetic compounds have been developed, which could be novel anticancer drugs. This review provides an overview on related articles and patents about AKR1B10 inhibitors, with a focus on their inhibition selectivity and mechanism of function.

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“…A purified flavonoid fraction prepared from RVS was found to have effective antiproliferative and apoptotic activities on various tumor cell lines including human lymphoma, breast cancer, osteosarcoma and transformed hepatoma cells [4,5,33,34]. Among these compounds, butein (3,4,2′,4′-tetrahydroxychalone) and sulfuretin are also suggested to have therapeutic value in suppressing cancer growth [35]. However, a synergistic effect of gemcitabine and aRVS extract was not observed in our study.…”

Section: Discussionmentioning

confidence: 99%

Efficacy and Safety of Standardized Allergen-Removed <i>Rhus verniciflua</i> Stokes Extract in Patients with Advanced or Metastatic Pancreatic Cancer: A Korean Single-Center Experience

et al. 2011

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Background: Pancreatic cancer has the worst prognosis because of poor response to conventional therapy. We investigated the clinical feasibility of the standardized allergen-removed Rhus verniciflua Stokes (aRVS) extract as a potential therapeutic agent for advanced or metastatic pancreatic cancer. Patients and Methods: From July 2006 to June 2010, patients with advanced or metastatic pancreatic adenocarcinoma were checked in our institution. After applying inclusion/exclusion criteria, 42 patients were eligible for the final analysis. Overall survival, clinical benefit and adverse events of these patients treated with aRVS in the aftercare period were determined. Results: In May 2011, 39 patients had died and the remaining 3 patients were alive with evidence of disease. The mean RVS administration period was 3.86 months (95% confidence interval 2.52–5.20). The median overall survival for the entire population was 7.87 months (95% confidence interval 5.14–10.59), and the 1-year survival rate was 26.2%, which is compatible with external controls. Using univariate and multivariate analyses, aRVS treatment including performance status and prognostic index significantly affected overall survival. A clinical benefit response was also shown by aRVS treatment which was not dependent on concurrent chemotherapy. Adverse reactions to aRVS treatment were mostly mild and self-limiting. Conclusions: The standardized aRVS extract might be beneficial for patients with advanced or metastatic pancreatic cancer since it positively affected overall survival and clinical symptoms without significant adverse effects.

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Inhibitory effects of polyphenols isolated from Rhus verniciflua on Aldo-keto reductase family 1 B10

Cited by 16 publications

References 24 publications

Identification of Aldo-Keto Reductase AKR1B10 as a Selective Target for Modification and Inhibition by Prostaglandin A1: Implications for Antitumoral Activity

Identification of Aldo-Keto Reductase AKR1B10 as a Selective Target for Modification and Inhibition by Prostaglandin A1: Implications for Antitumoral Activity

Aldo-Keto Reductase Family 1 Member B10 Inhibitors: Potential Drugs for Cancer Treatment

Efficacy and Safety of Standardized Allergen-Removed <i>Rhus verniciflua</i> Stokes Extract in Patients with Advanced or Metastatic Pancreatic Cancer: A Korean Single-Center Experience

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