Tamoxifen enhances erlotinib-induced cytotoxicity through down-regulating AKT-mediated thymidine phosphorylase expression in human non-small-cell lung cancer cells

Ko, Jen-Chung; Chiu, Hsien-Yi; Syu, Jhan-Jhang; Jian, Yi-Jun; Chen, Chien‐Yu; Jian, Yunting; Huang, Yi-Jhen; Wo, Ting-Yu; Lin, Yun‐Wei

doi:10.1016/j.bcp.2014.01.010

Cited by 27 publications

(17 citation statements)

References 42 publications

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“…Fulvestrant, another ER antagonist with no agonist effects, elicited significant tumor growth inhibition in an NSCLC xenograft model when it was used alone or in combination with other anti-cancer agents [9,40] . Previous studies demonstrated that TAM treatment inhibited cell survival in H520 and H1975 cells, while cotreatment with gefitinib plus TAM decreased proliferation and increased apoptosis in A549 and H1650 cells [41,42] . We demonstrated that TAM has anticancer and anti-estrogenic activity in NSCLC xenograft mice for the first time.…”

Section: Wwwchinapharcom Wang Lj Et Almentioning

confidence: 91%

Dexamethasone suppresses the growth of human non-small cell lung cancer via inducing estrogen sulfotransferase and inactivating estrogen

Wang

Hao

et al. 2016

Acta Pharmacol Sin

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Section: Wwwchinapharcom Wang Lj Et Almentioning

confidence: 91%

Dexamethasone suppresses the growth of human non-small cell lung cancer via inducing estrogen sulfotransferase and inactivating estrogen

Wang

Hao

et al. 2016

Acta Pharmacol Sin

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“…However, in mixtures, anticancer drugs are able to cause additive or synergistic effects at low concentrations (mg L À1 ) (Parrella et al, 2014b;Mi sík et al, 2016). Ko et al (2014) showed how in other eukaryotic models tamoxifen could enhance erlotinib-induced cytotoxicity through down-regulating AKT-mediated thymidine phosphorylase expression increasing the genotoxicity of the real samples. Similar results were obtained in the comet assay with ZFL cells, but in this case, significant correlations were obtained only for Pt and MET with MET included in the regression model.…”

Section: Correlation Between Chemical and Toxicological Characteristimentioning

confidence: 99%

Chemical and toxicological characterisation of anticancer drugs in hospital and municipal wastewaters from Slovenia and Spain

Isidori¹,

Lavorgna²,

Russo³

et al. 2016

Environmental Pollution

136

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Anticancer drugs are continuously released into hospital and urban wastewaters, where they, most commonly, undergo conventional treatment in wastewater treatment plants (WWTPs). Wastewaters contain complex mixtures of substances including parent compounds, their metabolites and transformation products (TPs). In this study, samples of hospital effluents and WWTP influents and effluents from Slovenia and Spain were analyzed for twenty-two selected anticancer drugs, their metabolites and transformation products. Acute and chronic toxicity tests were performed on the crustacean Ceriodaphnia dubia, genotoxicity was determined with Tradescantia and Allium cepa micronucleus (MN) assays and in vitro comet assay in zebrafish (Danio rerio) liver cell line (ZFL cells). Sixty of the two hundred-twenty determinations revealed detectable levels of anticancer drug residues. Among the targeted compounds, platinum based were most frequently detected (90%). Furthermore, erlotinib was detected in 80%, cyclophosphamide and tamoxifen in 70% and methotrexate in 60% of the samples. Seven of ten samples were toxic to C. dubia after acute exposure, whereas after chronic exposure all samples reduced reproduction of C. dubia at high sample dilutions. Allium cepa proved insensitive to the potential genotoxicity of the tested samples, while in Tradescantia increased MN frequencies were induced by a hospital effluent and WWTP influents. In ZFL comet assay all but one sample induced a significant increase of DNA strand breaks. Correlations of chemotherapeutics or their TPs were detected for all bioassays except for Allium cepa genotoxicity test, however for each test the highest correlations were found for different substances indicating differential sensitivities of the test organisms.

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“…Tamoxifen has been shown active in combination with cisplatin in non-small cell lung cancer [56] and recently demonstrated to enhance erlotinib-induced cytotoxicity in non-small cell lung cancer [57]; interestingly, compared to single agent erlotinib, the combination reduced activation of phospho-AKT and phospho-ERK 1/2 and reduced thymidine phosphorylase levels, underscoring the implications of tamoxifen in rational design of novel drug regimens. Moreover, favorable responses in glioma are believed to be linked to the interaction of tamoxifen with protein kinase C (PKC) [58].…”

Section: Non-sphingolipid-associated Activities Of Tpe’smentioning

confidence: 99%

Tamoxifen regulation of sphingolipid metabolism—Therapeutic implications

Morad

Cabot

2015

Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biolog

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Tamoxifen, a triphenylethylene antiestrogen and one of the first-line endocrine therapies used to treat estrogen receptor-positive breast cancer, has a number of interesting, off-target effects, and among these is the inhibition of sphingolipid metabolism. More specifically, tamoxifen inhibits ceramide glycosylation, and enzymatic step that can adventitiously support the influential tumor-suppressor properties of ceramide, the aliphatic backbone of sphingolipids. Additionally, tamoxifen and metabolites N-desmethyltamoxifen and 4-hydroxytamoxifen, have been shown to inhibit ceramide hydrolysis by the enzyme acid ceramidase. This particular intervention slows ceramide destruction and thereby depresses formation of sphingosine 1-phosphate, a mitogenic sphingolipid with cancer growth-promoting properties. As ceramide-centric therapies are becoming appealing clinical interventions in the treatment of cancer, agents like tamoxifen that can retard the generation of mitogenic sphingolipids and buffer ceramide clearance via inhibition of glycosylation, take on new importance. In this review, we present an abridged, lay introduction to sphingolipid metabolism, briefly chronicle tamoxifen’s history in the clinic, examine studies that demonstrate the impact of triphenylethylenes on sphingolipid metabolism in cancer cells, and canvass works relevant to the use of tamoxifen as adjuvant to drive ceramide-centric therapies in cancer treatment. The objective is to inform the readership of what could be a novel, off-label indication of tamoxifen and structurally-related triphenylethylenes, an indication divorced from estrogen receptor status and one with application in drug resistance.

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Tamoxifen enhances erlotinib-induced cytotoxicity through down-regulating AKT-mediated thymidine phosphorylase expression in human non-small-cell lung cancer cells

Cited by 27 publications

References 42 publications

Dexamethasone suppresses the growth of human non-small cell lung cancer via inducing estrogen sulfotransferase and inactivating estrogen

Dexamethasone suppresses the growth of human non-small cell lung cancer via inducing estrogen sulfotransferase and inactivating estrogen

Chemical and toxicological characterisation of anticancer drugs in hospital and municipal wastewaters from Slovenia and Spain

Tamoxifen regulation of sphingolipid metabolism—Therapeutic implications

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