Indoleamine 2,3-dioxygenase in melanoma progression and BRAF inhibitor resistance

Sandri, Silvana; Watanabe, Luis Roberto Masao; Oliveira, Érica Aparecida de; Faião-Flores, Fernanda; Migliorini, Silene; Tiago, Manoela; Felipe-Silva, Aloísio; Vazquez, Vinícius de Lima; Souza, Paola da Costa; Consolaro, Márcia Edilaine Lopes; Čampa, Ana; Maria‐Engler, Silvya Stuchi

doi:10.1016/j.phrs.2020.104998

Cited by 10 publications

(4 citation statements)

References 61 publications

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“…Melanoma cells were maintained in Dulbecco’s modified Eagle’s medium (DMEM; Sigma, St. Louis, MI, USA) with 4500 mg/L glucose and 4 mM L-glutamine supplemented with 10% fetal bovine serum (FBS; Gibco, Middlesex County, MA, USA) and 1% penicillin-streptomycin solution (Sigma Aldrich, St. Louis, MI, USA) at 37 °C and 5% CO 2 . Their PLX-resistant counterparts, A375R and SKMEL28R, were established as previously described [ 80 , 81 , 82 ]. In short, naïve A375 and SKMEL28 cell lines were plated onto 60 mm plates at a density of 1 × 10 4 cells and treated with 0.5–6 µM PLX every 3 days for 4–6 weeks.…”

Section: Methodsmentioning

confidence: 99%

3-Bromopyruvate Suppresses the Malignant Phenotype of Vemurafenib-Resistant Melanoma Cells

Vital

Bonatelli

Dias

et al. 2022

IJMS

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(1) BRAF mutations are associated with high mortality and are a substantial factor in therapeutic decisions. Therapies targeting BRAF-mutated tumors, such as vemurafenib (PLX), have significantly improved the overall survival of melanoma patients. However, patient relapse and low response rates remain challenging, even with contemporary therapeutic alternatives. Highly proliferative tumors often rely on glycolysis to sustain their aggressive phenotype. 3-bromopyruvate (3BP) is a promising glycolysis inhibitor reported to mitigate resistance in tumors. This study aimed to evaluate the potential of 3BP as an antineoplastic agent for PLX-resistant melanoma treatment. (2) The effect of 3BP alone or in combination with PLX on viability, proliferation, colony formation, cell death, migration, invasion, epithelial-mesenchymal marker and metabolic protein expression, extracellular glucose and lactate, and reactive species were evaluated in two PLX-resistant melanoma cell lines. (3) 3BP treatment, which was more effective as monotherapy than combined with PLX, disturbed the metabolic and epithelial-mesenchymal profile of PLX-resistant cells, impairing their proliferation, migration, and invasion and triggering cell death. (4) 3BP monotherapy is a potent metabolic-disrupting agent against PLX-resistant melanomas, supporting the suppression of the malignant phenotype in this type of neoplasia.

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Section: Methodsmentioning

confidence: 99%

3-Bromopyruvate Suppresses the Malignant Phenotype of Vemurafenib-Resistant Melanoma Cells

Vital

Bonatelli

Dias

et al. 2022

IJMS

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“…In turn, the administration of IDO inhibitors in combination therapy may increase their efficacy. Therefore, these agents are considered as a promising treatment strategy for lymphoma, melanoma, glioma, glioblastoma and head and neck squamous cell carcinomas ( Table 1 ) [ 83 , 105 , 106 , 107 , 108 , 109 , 118 , 119 , 134 , 137 , 151 ]. Indoximod is currently in clinical trials in combination with either temozolomide or bevacizumab for patients with GBM resistant to initial therapy and few objective responses have been observed [ 90 , 91 ].…”

Section: Modulation Of Kynurenine Pathway Activity In the Management Of Neoplastic Diseasesmentioning

confidence: 99%

“…[ 43 , 44 , 45 , 46 , 47 , 181 ]. Additionally, recent preclinical evidence indicates that the IDO1 inhibitors synergize the effects of tumor immuno- and chemotherapies and help to solve the problem of tumor resistance against them [ 83 , 93 , 105 , 106 , 107 , 108 , 112 , 113 , 119 , 120 , 129 , 132 , 133 , 136 , 137 , 143 , 146 , 151 , 154 , 155 , 156 , 157 , 171 ]. In turn, the discoveries concerning the role of IDO1 in tumor angiogenesis suggest that inhibiting its activity may effectively suppress this process, providing a potentially effective solution in the prevention of tumor development and metastasis.…”

Section: Summary and Future Directionsmentioning

confidence: 99%

Kynurenines as a Novel Target for the Treatment of Malignancies

2021

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Malignancies are unquestionably a significant public health problem. Their effective treatment is still a big challenge for modern medicine. Tumors have developed a wide range of mechanisms to evade an immune and therapeutic response. As a result, there is an unmet clinical need for research on solutions aimed at overcoming this problem. An accumulation of tryptophan metabolites belonging to the kynurenine pathway can enhance neoplastic progression because it causes the suppression of immune system response against cancer cells. They are also involved in the development of the mechanisms responsible for the resistance to antitumor therapy. Kynurenine belongs to the most potent immunosuppressive metabolites of this pathway and has a significant impact on the development of malignancies. This fact prompted researchers to assess whether targeting the enzymes responsible for its synthesis could be an effective therapeutic strategy for various cancers. To date, numerous studies, both preclinical and clinical, have been conducted on this topic, especially regarding the inhibition of indoleamine 2,3-dioxygenase activity and their results can be considered noteworthy. This review gathers and systematizes the knowledge about the role of the kynurenine pathway in neoplastic progression and the findings regarding the usefulness of modulating its activity in anticancer therapy.

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“…The development and application of immune regulators have also been extensively studied. 1MT is a blocker of IDO that has been promoted and applied in clinical trials ( 19 ) and can inhibit tryptophan degradation to kynurenine and increase the antitumor effect of functional T cells ( 20 , 21 ). Although IDO inhibitors are well tolerated, they yield a limited efficacy in cancer patients during clinical trials as monotherapy ( 22 ).…”

Section: Introductionmentioning

confidence: 99%

IDO Inhibitor and Gallic Acid Cross-Linked Small Molecule Drug Synergistic Treatment of Melanoma

Gao

Chen

et al. 2022

Front. Oncol.

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In this study, we synthesized a molecule GA-1MT (GM) composed of indoleamine 2,3-dioxygenase (IDO) inhibitor (1-methyl-d-tryptophan, 1MT) called NLG8189 and gallic acid (GA) and verified its therapeutic effect on B16F10 melanoma cells and an orthotopic tumor-bearing mouse model. The synthesized molecule GM was analyzed by 1H NMR and mass spectrometry (MS). In addition, we confirmed that GM could mediate the immune response in the B16F10 cell tumor model by flow cytometry and immunofluorescence. The synthesized GM molecule could increase the solubility of 1MT to enhance the drug efficacy and lower costs. Moreover, GM could inhibit melanoma growth by combining 1MT and GA. In vivo experiments showed that GM could effectively inhibit the expression of tyrosinase, regulate the proportion of CD4+ T cells, CD8+ T cells, and regulatory T cells (Treg cells) in tumors, and significantly suppress melanoma growth. The newly synthesized drug GM could more effectively inhibit melanoma than GA and 1MT alone or in combination.

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Indoleamine 2,3-dioxygenase in melanoma progression and BRAF inhibitor resistance

Cited by 10 publications

References 61 publications

3-Bromopyruvate Suppresses the Malignant Phenotype of Vemurafenib-Resistant Melanoma Cells

3-Bromopyruvate Suppresses the Malignant Phenotype of Vemurafenib-Resistant Melanoma Cells

Kynurenines as a Novel Target for the Treatment of Malignancies

IDO Inhibitor and Gallic Acid Cross-Linked Small Molecule Drug Synergistic Treatment of Melanoma

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