Inhibitory Effect of Turmeric Curcuminoids on FLT3 Expression and Cell Cycle Arrest in the FLT3-Overexpressing EoL-1 Leukemic Cell Line

Tima, Singkome; Ichikawa, Hideki; Ampasavate, Chadarat; Okonogi, Siriporn; Anuchapreeda, Songyot

doi:10.1021/np401028h

Cited by 20 publications

(17 citation statements)

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“…Moreover, CM exhibited a strong inhibitory effect on rate of proliferation as well as FLT3 and STAT5A protein expressions in EoL-1 cells. 16 Thus, the mechanism of CM action in EoL-1 and MV-4-11 cells might involve in the inhibition of STAT5A-induced cell proliferation. On the other hand, FLT3 causes the activation of phosphatidylinositol-3-kinase (PI3K) which stimulates protein kinase B or AKT protein that regulates many downstream proteins involve in cell survival and anti-apoptosis.…”

Section: Resultsmentioning

confidence: 99%

“…14,15 In a recent study, CM exhibited an excellent cytotoxic effect, induced cell cycle arrest, and demonstrated the strong inhibitory effect on FLT3 protein in FLT3-overexpressing EoL-1 leukemic cells. 16 Although CM has many biological properties, the low water solubility is a major barrier to its clinical applications. 17 …”

Section: Introductionmentioning

confidence: 99%

“…43 Although there are numerous FLT3 inhibitors and antibodies that have been developed since the last decade, only a small number of FLT3-specific nanoparticles were reported. 44 According to anti-leukemia properties of CM on FLT3-overexpressing leukemic cells 16 and the effectiveness of drug delivery system (DDS) with target-specific nanoparticles, this study aims to produce FLT3-CM-micelles with surface FLT3-specific peptides, evaluate their properties, and investigate their cytotoxic effect on FLT3-overexpressing leukemic cell lines.…”

Section: Introductionmentioning

confidence: 99%

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Development and Characterization of FLT3-Specific Curcumin-Loaded Polymeric Micelles as a Drug Delivery System for Treating FLT3-Overexpressing Leukemic Cells

Tima

Okonogi

Ampasavate

et al. 2016

Journal of Pharmaceutical Sciences

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This study aimed to develop a curcumin (CM) nanoparticle targeted to Feline McDonough Sarcoma (FMS)-like tyrosine kinase 3 (FLT3) protein on the surface of leukemic cells and to evaluate their properties, specificity, cytotoxicity, and inhibitory effect on FLT3 protein level in FLT3 overexpressing leukemic cells, EoL-1 and MV-4-11 cells. FLT3-specific peptides were conjugated onto modified poloxamer 407 (P407) using the copper-catalyzed azide-alkyne cycloaddition reaction (CuAAC). The thin film hydration method was performed for FLT3-specific CM-loaded polymeric micelles (FLT3-CM-micelles) preparation. Flow cytometry and fluorescence microscopy were used to determine rate of cellular uptake. 3-(4,5-dimethythiazol-2-yl)-2,5-diphenyl tetrazolium bromide assay was used to test the cytotoxicity of the micelles on leukemic cells. FLT3-CM-micelles demonstrated a mean particle size less than 50 nm, high entrapment efficiency, and high rate of CM uptake by leukemic cells. The intracellular CM fluorescence is related to FLT3 protein levels on the leukemic cell surfaces. Moreover, FLT3-CM-micelles demonstrated an excellent cytotoxic effect and decreased FLT3 protein expression in the leukemic cells. The FLT3-CM-micelles could enhance both solubility and cytotoxicity of CM on FLT3 overexpressing leukemic cells. These promising nanoparticles may be used for enhancing anti-leukemic activity of CM and developed as a targeted drug delivery system in the future.

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Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Development and Characterization of FLT3-Specific Curcumin-Loaded Polymeric Micelles as a Drug Delivery System for Treating FLT3-Overexpressing Leukemic Cells

Tima

Okonogi

Ampasavate

et al. 2016

Journal of Pharmaceutical Sciences

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“…Another classis combination is DOX and CUR. CUR was believed to inhibit the tumor growth by causing cell cycle arrest [133,134], inducing an apoptotic signal [135,136], reversing multidrug resistance [137] and inhibiting the activation of NF-κB [138,139]. The exact molecular mechanisms of curcumin-induced apoptosis in cancer cells varied and depended on the cell type and dose used [140].…”

Section: Dose/efficacy Relationship Within Co-delivery Systemsmentioning

confidence: 99%

Polymeric Co-Delivery Systems in Cancer Treatment: An Overview on Component Drugs’ Dosage Ratio Effect

et al. 2019

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Multiple factors are involved in the development of cancers and their effects on survival rate. Many are related to chemo-resistance of tumor cells. Thus, treatment with a single therapeutic agent is often inadequate for successful cancer therapy. Ideally, combination therapy inhibits tumor growth through multiple pathways by enhancing the performance of each individual therapy, often resulting in a synergistic effect. Polymeric nanoparticles prepared from block co-polymers have been a popular platform for co-delivery of combinations of drugs associated with the multiple functional compartments within such nanoparticles. Various polymeric nanoparticles have been applied to achieve enhanced therapeutic efficacy in cancer therapy. However, reported drug ratios used in such systems often vary widely. Thus, the same combination of drugs may result in very different therapeutic outcomes. In this review, we investigated polymeric co-delivery systems used in cancer treatment and the drug combinations used in these systems for synergistic anti-cancer effect. Development of polymeric co-delivery systems for a maximized therapeutic effect requires a deeper understanding of the optimal ratio among therapeutic agents and the natural heterogenicity of tumors.

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“…Entretanto em 48 horas não observou-se diferença com relação ao controle devido à baixa estabilidade da curcumina (TIMA et al, 2014).…”

Section: Establidade Do Dm-1 Em Solvente Orgânico E Aquosounclassified

Efeitos citotóxicos do DM-1 em células de melanoma resistentes a um inibidor de BRAF e na expressão de metaloproteinases

Souza¹

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Palavras-chave: melanoma, inibição de BRAFV600E, análogos da curcumina, metalloproteinase, invasão. ABSTRACT SOUZA, Nayane de. DM-1 cytotoxic effects in BRAF resistant melanoma cell lines and metalloproteinase expression modulation. 2017. 130p. Dissertação (Mestrado)-Faculdade de Ciências Farmacêuticas, São Paulo, 2017. Malignant melanoma is the most aggressive cancer and the BRAF V600E mutation is the most frequent among patients. Vemurafenib was the first specific inhibitor for this mutation approved by Food and Drug Administration. Therefore around six months later there is relapse and overcoming it is still a challenge. Curcumin is a turmeric and it has been deeply researched because of its anti-inflammatory and antitumoral effects. However the low stability limits its use, therefore, encouraged the investigation of analogues capable to be efficient and commercialized. DM-1 is a monoketone curcumin analog and it showed antitumoral effects in vitro and in vivo in previous studies The aim of this project was to evaluate the cytotoxical effects of DM-1 for vemurafenib responsive (naïve) and resistant melanoma cells, as well as metalloproteinases modulation. Melanoma cells were treated with different DM-1 concentrations, and this compound was cytotoxic for responsive and resistant cell lines, besides inducing G1/G0 cell cycle arrest and reducing the number of colonies, nonetheless it was not selective in assays performed with melanocytes and fibroblasts. Subtoxic treatment of those cells modulated important MMPs in the cell invasion process. DM-1 reduced metalloproteinases-1,-2 and-9 (MMP-1,-2 and-9) in a quantification assay, and MMP-2 and-9 activities by zymography in a cell-dependent way. Negative modulations of MMP inhibitor TIMP-2 and MMP-14 for SKMEL-28 naïve were associated with MMP-2 and-9 reduced activities, whereas positive modulations for SKMEL-19 naïve were correlated to MMP-2 increase. Furthermore, this compound reduced migration of those cells and endothelial cell tube formation.

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Inhibitory Effect of Turmeric Curcuminoids on FLT3 Expression and Cell Cycle Arrest in the FLT3-Overexpressing EoL-1 Leukemic Cell Line

Cited by 20 publications

References 20 publications

Development and Characterization of FLT3-Specific Curcumin-Loaded Polymeric Micelles as a Drug Delivery System for Treating FLT3-Overexpressing Leukemic Cells

Development and Characterization of FLT3-Specific Curcumin-Loaded Polymeric Micelles as a Drug Delivery System for Treating FLT3-Overexpressing Leukemic Cells

Polymeric Co-Delivery Systems in Cancer Treatment: An Overview on Component Drugs’ Dosage Ratio Effect

Efeitos citotóxicos do DM-1 em células de melanoma resistentes a um inibidor de BRAF e na expressão de metaloproteinases

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