Proteomic identification of aldo-keto reductase AKR1B10 induction after treatment of colorectal cancer cells with the proteasome inhibitor bortezomib

Löffler‐Ragg, Judith; Mueller, Doris; Gamerith, Gabriele; Auer, T.; Skvortsov, Sergej; Sarg, Bettina; Skvortsova, Ira; Schmitz, Klaus; Martin, H.; Krugmann, Jens; Alakus, Hakan; Maser, Edmund; Menzel, J.; Hilbe, Wolfgang; Lindner, Herbert; Schmid, Kurt Werner; Zwierzina, Heinz

doi:10.1158/1535-7163.mct-08-0987

Cited by 24 publications

(20 citation statements)

References 48 publications

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“…1A) on AML cell proliferation, we set up serial concentrations of 2 drugs based on clinical pharmacokinetic studies (bortezomib < 100 nmol/ L, ATRA 1 mmol/L; refs. [15][16][17] and determined that bortezomib showed distinct synergy with ATRA in HL60 and NB4 cell lines, with most combination index (CI) values below 0.8 ( Supplementary Fig. S1A and S1B).…”

Section: Bortezomib and Atra Synergistically Inhibited Cell Proliferamentioning

confidence: 99%

Bortezomib Sensitizes Human Acute Myeloid Leukemia Cells to All-Trans-Retinoic Acid–Induced Differentiation by Modifying the RARα/STAT1 Axis

Ying

Zhou

Zhong

et al. 2013

Molecular Cancer Therapeutics

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All-trans-retinoic acid (ATRA) has held great promise for differentiation-based therapy but reportedly downregulates retinoic acid receptor-a (RARa) in a proteasome-dependent manner, which leads to decreased acute myeloid leukemia (AML) cell differentiation efficiency. Therefore, research strategies that seek to further sensitize cells to retinoids and extend the range of retinoid-affected myeloid malignancies beyond acute promyelocytic leukemia (APL) are key investigative avenues. Here, we show that bortezomib, the first proteasome inhibitor approved for newly diagnosed and relapsed multiple myeloma, exhibited strong synergism with ATRA to promote HL60 and NB4 AML cell differentiation. We observed that bortezomib sensitized AML cells to ATRA-induced morphologic, biochemical, and functional changes, indicative of myeloid differentiation without cell death. In addition, treatment of human leukemia HL60 xenografts with bortezomib and ATRA together did not increase bortezomib-induced progressive weight loss but resulted in significant tumor growth inhibition in addition to increased differentiation (P < 0.05). These enhanced differentiation effects were accompanied by RARa stabilization and STAT1 activation. Taken together, our study was the first to evaluate bortezomib and ATRA synergy in AML cell differentiation and to assess new opportunities for bortezomib and ATRA combination as a promising approach for future differentiation therapy. Mol Cancer Ther; 12(2); 195-206. Ó2012 AACR.

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Section: Bortezomib and Atra Synergistically Inhibited Cell Proliferamentioning

confidence: 99%

Bortezomib Sensitizes Human Acute Myeloid Leukemia Cells to All-Trans-Retinoic Acid–Induced Differentiation by Modifying the RARα/STAT1 Axis

Ying

Zhou

Zhong

et al. 2013

Molecular Cancer Therapeutics

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“…Bortezomib causes upregulation of AKR1B10, and this finding may explain its potential chemotherapeutic role in colorectal carcinomas. 9 The above examples clearly illustrate the role of AKR1B10 in tumor carcinogenesis and the need for further large-scale studies to fully elaborate its role and prognostic significance in other tumors.…”

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confidence: 96%

AKR1B10 and its emerging role in tumor carcinogenesis and as a cancer biomarker

Kapoor¹

2012

Intl Journal of Cancer

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I read with great interest the recent article by Ma et al. in a recent issue of your esteemed journal.1 The article is highly thought provoking. Interestingly, new data have recently emerged over the past few years that implicate AKR1B10 in tumor carcinogenesis in different systemic malignancies besides breast carcinomas.For instance, increased expression of AKR1B10 is seen in nearly 84% of squamous cell pulmonary carcinomas.2 In fact, a close co-relation exists between AKR1B10 expression by lung cancers and smoking habits.3 AKR1B10 is therefore rapidly emerging as a sensitive marker of nonsmall cell lung carcinomas especially in smokers. 4 Similarly, AKR1B10 alters prenylation of pancreatic proteins. As a result, tumor carcinogenesis is accentuated in pancreatic carcinomas. In fact, 70% of pancreatic adenocarcinomas demonstrate increased AKR1B10 expression, thus making AKR1B10 a potential biomarker of pancreatic malignancies. 5AKR1B10 is also emerging as a prognostic biomarker of hepatocellular carcinomas. For instance, a better prognostic outcome is seen with accentuated AKR1B10 expression. 6Increased AKR1B10 expression is especially associated with underlying cirrhosis and viral-mediated hepatocellular carcinomas. AKR1B10 expression also serves as a prognostic biomarker of bladder carcinogenesis. For instance, postcystectomy patients who receive dual gemcitabine and carboplatin therapy and express AKR1B10 generally tend to have a poor clinical outcome.7 Attenuated AKR1B10 expression in colonic tissue also serves as a marker of carcinogenesis in these tissues. In fact, downregulated AKR1B10 levels are seen in nearly 88% of colorectal carcinomas.8 Simultaneous attenuation of AKR1B1 is seen in 10% of colorectal carcinomas. Bortezomib causes upregulation of AKR1B10, and this finding may explain its potential chemotherapeutic role in colorectal carcinomas. 9The above examples clearly illustrate the role of AKR1B10 in tumor carcinogenesis and the need for further large-scale studies to fully elaborate its role and prognostic significance in other tumors.

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“…An outstanding feature of AKR1B10 is its up-regulation in lung and hepatic carcinomas (squamous cell carcinoma and adenocarcinoma), 15,20) as well as in esophageal, uterine and colorectal cancers, [21][22][23] indicating its potential role as a tumor marker. The enzyme is suggested to participate in the cell carcinogenesis and tumor development by detoxifying cytotoxic carbonyls, 16,24) mediating retinoic acid homeostasis, 18,25) and regulating cellular fatty acid synthesis and lipid metabolism.…”

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confidence: 99%

Selective Inhibition of the Tumor Marker AKR1B10 by Antiinflammatory N-Phenylanthranilic Acids and Glycyrrhetic Acid

Endo

Matsunaga

Soda

et al. 2010

Biological & Pharmaceutical Bulletin

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A human aldose reductase-like protein, AKR1B10 in the aldo-keto reductase (AKR) superfamily, was recently identified as a tumor marker of several types of cancer. Tolrestat, an aldose reductase inhibitor (ARI), is known to be the most potent inhibitor of the enzyme. In this study, we compared the inhibitory effects of other ARIs including flavonoids on AKR1B10 and aldose reductase to evaluate their specificity. However, ARIs showed lower inhibitory potency for AKR1B10 than for aldose reductase. In the search for potent and selective inhibitors of AKR1B10 from other drugs used clinically, we found that non-steroidal antiinflammatory N-phenylanthranilic acids, diclofenac and glycyrrhetic acid competitively inhibited AKR1B10, showing K i values of 0.35-2.9 m mM and high selectivity to this enzyme (43-57 fold versus aldose reductase). Molecular docking studies of mefenamic acid and glycyrrhetic acid in the AKR1B10-nicotinamide adenine dinucleotide phosphate (NADP ؉ ؉ ) complex and site-directed mutagenesis of the putative binding residues suggest that the side chain of Val301 and a hydrogen-bonding network among residues Val301, Gln114 and Ser304 are important for determining the inhibitory potency and selectivity of the non-steroidal antiinflammatory drugs. Thus, the potent and selective inhibition may be related to the cancer chemopreventive roles of the drugs, and their structural features may facilitate the design of new anti-cancer agents targeting AKR1B10.

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Proteomic identification of aldo-keto reductase AKR1B10 induction after treatment of colorectal cancer cells with the proteasome inhibitor bortezomib

Cited by 24 publications

References 48 publications

Bortezomib Sensitizes Human Acute Myeloid Leukemia Cells to All-Trans-Retinoic Acid–Induced Differentiation by Modifying the RARα/STAT1 Axis

Bortezomib Sensitizes Human Acute Myeloid Leukemia Cells to All-Trans-Retinoic Acid–Induced Differentiation by Modifying the RARα/STAT1 Axis

AKR1B10 and its emerging role in tumor carcinogenesis and as a cancer biomarker

Selective Inhibition of the Tumor Marker AKR1B10 by Antiinflammatory N-Phenylanthranilic Acids and Glycyrrhetic Acid

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